Mineral Elements Micro Trace

Thyroid Factor

The Natural Thyroid Diet

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Xin Gen Lei

Cornell University, Ithaca, New York, U.S.A. Hong Yang

ADM Alliance Nutrition, Inc., Quincy, Illinois, U.S.A.

INTRODUCTION

Trace minerals are so named because they exist in the body at concentrations of <0.001% and animals require them in diets at <100 mg/kg of feed. Up to the early 1950s, only six trace elements (iron, iodine, copper, manganese, zinc, and cobalt) were identified as nutritionally essential. In 1957, selenium was added to the list. At present, another eight elements including boron, chromium, lithium, molybdenum, nickel, silicon, tin, and vanadium are considered occasionally beneficial or conditionally essential. Six elements including aluminum, arsenic, cadmium, fluorine, lead, and mercury are considered essentially toxic.[2] There is controversy as to whether elements such as arsenic and fluorine should also be classified as conditionally essential or simply as toxic. However, it is clear that copper, iodine, iron, manganese, selenium, and zinc are absolutely essential to domestic animals, and have the most practical significance. Cobalt is required by all species as a constituent of vitamin B12. The chemical properties, major functions, deficiency and toxicity symptoms, requirements, maximal tolerable levels, and sources of seven trace elements are summarized in Table 1.

GENERAL FUNCTIONS

The best characterized and probably the most important function of trace elements is their catalytic roles in enzyme and hormone systems. As presented in Table 1, these elements serve as: 1) integral components of metalloenzymes such as copper, zinc, and manganese in superoxide dismutases or selenium in glutathione perox-idase; 2) activators or inhibitors of certain enzymes; and 3) structure components of hormones or their complexes such as iodine in thyroid hormones and zinc in insulin. Certain trace elements are essential components of metabolically important compounds such as iron in hemoglobin and cobalt in vitamin B12. Although trace elements, similar to the macro ones, are normally detectable in bone and other organs or tissues, it is unclear whether they have any structural or electrolytic essentiality other than the aforementioned biocatalyst roles. In addition, a number of elements have been shown to be important for body immune functions, but their mechanism remains to be elucidated.

DOSE-DEPENDENT RESPONSES AND METABOLISM

Unlike other nutrients, trace elements cannot be generated in the body by de novo synthesis. Animals need to regularly ingest them from their diets or they may deplete their body store and develop deficiency (Table 1). Homeostatic regulations of trace elements in animals are largely unclear, but probably occur mainly through absorption. Specific metal transporters such as divalent metal transporter-I have been characterized. Meanwhile, urine, skin, hair, and breath also contribute to the loss of certain elements. The nutrient requirements of trace minerals by animals define the lower limits of dietary adequacy. These requirements are established by relating responses of specific biochemical indicators, growth or performance, and health to graded levels of dietary mineral concentrations. Deficiency occurs when trace element levels in diets are lower than required and animals do not receive nonoral supplementation. In contrast, excessive minerals in diets cause toxicity. The toxic levels of individual elements appear to be highly variable, ranging between 10 and 1500 times of the recommended adequate levels.[4] For some elements, dietary levels between the adequate and the toxic levels may have pharmacological effects. A good example is that high levels of copper (125 250 mg/kg of diet as sulfate) or zinc (up to 3000 mg/kg of diet as oxide) have been shown to promote growth and to help control gut pathogens. However, their effects are not additive in diets for weanling pigs,[5] and there are environmental concerns associated with such high dietary levels of metals.

Table 1 Chemical and nutritional properties of practically important trace elements

Cobalt

Copper

Iodine

Iron

Atomic

27

29

53

26

number

Atomic

58.9

63.5

126.9

55.9

weight

Major

A cofactor of

A component of

A component of

A component of

functions

vitamin B12j

metalloenzymes

thyroid hormones,

hemoglobin,

involved in

(cytochrome C

involved in

myoglobin,

one-carbon

oxidase, lysyl

regulation of

cytochromes, and

unit metabolism

oxidase, superoxide

metabolic rate,

enzymes

dismutase,

protein synthesis,

(catalase, etc.),

tyrosinase, etc.),

reproduction,

involved in oxygen

involved in cellular

and mental

and electron

respiration,

development

transport and

cross-linking of

peroxide breakdown

connective tissues,

pigmentation,

integrity

of central nervous

system, immune

function,

reproduction,

and lipid

metabolism

Typical

Similar to

Anemia, anoxia,

Goiter, myxedema,

Anemia,

deficiency

vitamin B12

ataxia, aortic

impaired

poor growth,

signs

deficiency:

rupture,

reproduction,

pallor, rough

anemia, lack

bone disorders,

postnatal mortality,

hair coat, anoxia,

of appetite,

depigmentation,

growth retardation,

fatty liver, and

poor growth,

loss of appetite

and integument

enlarged heart

wasting away

disorders

and spleen,

loss of appetite

54.9

Manganese

Selenium

Zinc

54.9

79.0

A component of pyruvate carboxylase, superoxide dismutase, and glycosylamino transferases, involved in lipid and carbohydrate metabolism, cartilage development, blood clotting, antioxidation, reproduction and immune functions

A component of at least 15 enzymes such as glutathione peroxidase, involved in protecting biological membranes, proteins, and lipids from oxidative degeneration; important for thyroid hormone metabolism and reproduction; closely linked to vitamin E function

Skeletal abnormalities, perosis (chicks), ataxia, reproductive disorders, poor growth and appetite

White muscle disease (ruminants), exudative diathesis and pancreatic atrophy (chicks); liver necrosis and mulberry heart disease (pigs)

30 65.4

A component of >200 enzymes involved in DNA synthesis, nucleic acid, protein, lipid, carbohydrate, and vitamin metabolism; interact with insulin and other hormones; specific effect on gene expression, appetite, and skin and wound healing; essential for growth, reproduction, and immune functions

Abrupt loss of appetite and growth, parakeratosis, skeletal and reproductive disorders, reduced thymus weight

Toxicity

Anorexia, growth depression, emaciation, anemia, hyper-

chromemia, and debility

Nausea, vomiting, icterus, anemia, impaired growth and reproduction, paralysis, collapse and death

Depression, anorexia, listless, eye lesions, impaired immune function, hypothermia

Anorexia, diarrhea, rickets, oliguria, diphasic shock, hypothermia, metabolic acidosis and death

Reduced growth and appetite, anemia, stiffness of limbs and stilted gait

Alkali disease (grazing animals), anorexia, hair loss, hoof separation, depression, emaciation, death

Reduced growth and feed intake, arthritis, gastritis, enteritis

Requirementa Cattle

0.1

10

0.50

50

20^10

0.1

30

Poultry

NRb

4—8

0.35

38-80

17-60

<0.2

29-70

Swine

NR

3-6

0.14

40-100

2-20

0.3

50-100

MTLC

Cattle

10

100

50

1000

1000

(2)

500

Poultry

10

300

300

1000

2000

2

1000

Swine

10

250

400

3000

400

2

1000

Sheep

10

25

50

500

1000

(2)

300

Common

Carbonate,

Sulfate, oxide,

Calcium iodate,

Sulfate, oxide,

Sulfate, oxide,

Sodium selenate

Sulfate, oxide,

sulfate, chloride, and oxide

(for ruminants)

and organic potassium iodide, and EDDId carbonate, and organic and organic or selenite; Se-enriched yeast and organic sulfate, chloride, and oxide

(for ruminants)

and organic potassium iodide, and EDDId carbonate, and organic and organic or selenite; Se-enriched yeast and organic

"Requirement=Values (mg/kg of diet) are taken from NRC (National Research Council) standards bNR=No recommendations have been made by NRC The levels in parentheses were derived by interspecies extrapolation CMTL=Maximal tolerable level (mg/kg of diet) dEDDI=Ethylene diamine dihydro-iodide

SOURCES

Trace elements are normally supplemented into animal diets as inorganic salts, primarily as oxide, sulfate, and carbonate. Bioavailability of any given element in these salts is generally high, but varies with the form of salt. Caution should be given to acid base balance in formulating diets using various forms of trace mineral salts. Recently, a number of organic forms of trace element supplements have been developed, due to the increasing interests in improving bioavailability of trace elements to animals, in reducing their concentrations in animal excreta, and in enriching their contents in animal products for human health. According to the Association of American Feed Control Officials (AAFCO), there are five basic types of organic trace mineral complexes: metal polysaccharide complex, metal proteinate, metal amino acid complex, metal (specific amino acid) complex, and metal amino acid chelate. A limited amount of research has shown the benefit of these organic forms of trace minerals over their inorganic salts to animal nutrition and environment. However, further research is certainly warranted to confirm consistency of these benefits.

INTERACTIONS

It is well known that trace elements interact with each other, but the molecular mechanism and the physiological impacts of those interactions are far from clear. Simply speaking, different elements interact at sites of absorption, transport, metabolism, and function. A large portion of copper and zinc is presumably absorbed in the small intestine via the same protein carrier. Thus excess of zinc can induce a deficiency of copper. Mobilization of iron from storage for hemoglobin synthesis requires a copper-containing enzyme. Selenium-dependent iodothyronine 5'-deiodinase catalyzes the deiodination of thyroxine to the active 3,3',5-triiodothyronine. As a result, selenium deficiency impairs iodine function. Meanwhile, antagonistic interactions between minerals such as selenium and arsenic or cobalt and iron can be used to alleviate the toxicity of each other.[1,3]

NEW PARADIGM

Traditionally, metabolic functions and nutrient requirements of trace elements have been studied using purified or natural diets deficient in a specific element. Because of the functional and metabolic complexity of trace elements, this conventional deficiency model does not give specific biochemical explanations to many clinical symptoms. In some cases, deficiency is not easy to produce. Recent advances in molecular biology have enabled scientists to determine the effects of trace elements on gene and protein expression, signal transduction, and metabolic functions at the molecular, cellular, and genomic levels.[6] The development of transgenic and gene-knockout animal models allows for the determination of specific functions of individual trace element dependent or related proteins. A successful example is the use of selenium-dependent glutathione peroxidase-1 knockout mice to study the contribution of this particular enzyme to the total function of selenium.[7] These models can be applied to check the presumed functions of the established essential elements and to help in determining nutritional significance of those less well-characterized elements.

CONCLUSION

Seven trace elements have been well characterized as nutritionally essential to farm animals. The nutrient requirements of these elements by different species and their deficiency symptoms are better understood than the biochemical and molecular mechanisms for their physiological functions. Various organic complexes of trace elements have been developed to improve their bioavail-ability to animals and to reduce their excretion by animals to the environment.

REFERENCES

1. McDowell, L.R. Minerals in Animals and Human Nutrition; Academic Press: San Diego, CA, 1992.

2. Underwood, E.J.; Suttle, N.F. The Mineral Nutrition of Livestock, 3rd Ed.; CABI Publishing: New York, 1999.

3. Nelssen, J.L.; Miller, E.R.; Henry, S.C. Chapter 60: Nutrition, Deficiencies and Dietetics. In Disease of Swine; Leman, A.D., Straw, B.E., Mengeling, W.L., D'Allaire, S., Taylor, D.J., Eds.; Iowa State University Press: Ames, IA, 1992; 744 755.

4. NRC. Mineral Tolerance of Domestic Animals; National Academy Press, National Academy of Sciences: Washing ton, DC, 1980.

5. Hill, G.M.; Cromwell, G.L.; Crenshaw, T.D.; Dove, C.R.; Ewan, R.C.; Knabe, D.A.; Lewis, A.J.; Libal, G.W.; Mahan, D.C.; Shurson, G.C.; Southern, L.L.; Veum, T.L. Growth promotion effects and plasma changes from feeding high dietary concentrations of zinc and copper to weanling pigs (regional study). J. Anim. Sci. 2000, 78, 1010 1016.

6. O'Dell, B.L.; Sunde, R.A. Handbook of Nutritionally Essential Mineral Elements; Mercel Dekker, Inc.: New York, NY, 1997.

7. Lei, X.G. Chapter 19: In vivo Antioxidant Role of GPX1: Evidence From the Knockout Mice. In Protein Sensors of Reactive Oxygen Species: Selenoproteins, Thioredoxin, Thiol Enzymes, and Proteins; Sies, H., Packer, L., Eds.; Methods in Enzymology, Academic Press, 2002; Vol. 347, 21 225.

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