Trace Element Detector,TEL:0086-516-85751841

Early in the twentieth century, scientists were able to qualitatively detect small amounts of several elements in living organisms. At the time, these elements were often described as being present in "traces" or "trace amounts." This apparently led to the term "trace elements," which today is usually defined as mineral elements that occur in living systems in micrograms per gram of body weight or less. A majority of elements of the periodic table probably could be considered trace elements. However, the presence of most of these elements in higher animals quite likely is just a manifestation of our geochemical origin or the result of environmental exposure. Only eight trace elements are generally accepted as being essential for health and wellbeing in higher animals through the consumption of food and beverages; these are cobalt, copper, iodine, iron, manganese, molybdenum, selenium, and zinc. Persuasive evidence has recently appeared that indicates two other trace elements, boron and chromium, may also be essential; however, general acceptance of their essentiality is still lacking. Based on findings with experimental animals and lower life forms, numerous other trace elements have been suggested as being essential for higher animals including aluminum, arsenic, fluorine, lithium, nickel, silicon, and vanadium. However, conclusive evidence for essentiality, such as a defined biochemical function, is lacking for these elements. Thus, their nutritional importance remains to be determined. Of the elements mentioned, assuring the consumption of foods providing adequate amounts of iodine, iron, and zinc is of greatest practical concern for human health. Evidence is emerging, however, suggesting that the amount of cobalt (as vitamin B12), copper, selenium, boron, and chromium provided through foods should be considered a practical nutritional concern in assuring or promoting health and well-being. These eight elements will be emphasized in this review.

Physiological Roles of Trace Elements

Trace elements have several roles in living organisms. Some are essential components of enzymes where they attract substrate molecules and facilitate their conversion to specific end products. Some donate or accept electrons in reactions of reduction and oxidation, which results in the generation and utilization of metabolic energy. One trace element, iron, is involved in the binding, transporting, and releasing of oxygen in higher animals. Some trace elements impart structural stability to important biological molecules. Finally, some trace elements control important biological processes through such actions as facilitating the binding of molecules to receptor sites on cell membranes, altering the structure or ionic nature of membranes to prevent or allow specific molecules to enter or leave a cell, and inducing gene expression resulting in the formation of proteins involved in life processes.

Homeostatic Regulation of Trace Elements

The ability of the body to maintain the content of a specific substance such as a trace element within a certain range despite varying intakes is called homeostasis. Homeostasis involves the processes of absorption, storage, and excretion. The relative importance of these three processes varies among the trace elements. The homeostatic regulation of trace elements existing as positively charged cations (for example, copper, iron, zinc) occurs primarily during absorption from the gastrointestinal tract. Trace elements absorbed as negatively charged anions (for example, boron, selenium) are usually absorbed freely and completely from the gastrointestinal tract. Thus, they are homeostatically regulated primarily by excretion through the urine, bile, sweat, and breath. Storage of trace elements in inactive sites or forms is another mechanism that prevents inappropriate amounts of reactive trace elements to be present, for example, storage of iron in the form of ferritin. Release of a trace element from a storage site also can be important in preventing deficiency.

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About Trace Element Detection

Iodine

This trace element has one known function in higher animals and humans; it is a constituent of thyroid hormone (thyroxine, T4) that, after conversion to triiodothyronine (T3), functions as a regulator of growth and development by reacting with cell receptors, which results in energy (adenosine triphosphate, ATP) production and the activation or inhibition of synthesis of specific proteins.

Recognition that iodine was nutritionally important began in the 1920s when it was found that iodine prevented goiter, and increased iodine intake was associated with decreased endemic cretinism, the arrested physical and mental development caused by the lack of thyroid hormone. Today, the consequences of iodine deficiency still are a major public health problem in the world. In fact, iodine deficiency is the most prevalent global cause of preventable mental retardation. Briefly, the spectrum of iodine deficiency disorders is large and includes fetal congenital anomalies and perinatal mortality; neurological cretinism characterized by mental deficiency, deaf mutism, spastic diplegia (spastic stiffness of the limbs), and squint; psychomotor defects; goiter; and slowing of the metabolic rate causing fatigue, slowing of bodily and mental functions, weight increase, and cold intolerance.

Although homeostatic mechanisms allow for a substantial tolerance to high intakes of iodine, iodine-induced hyperthyroidism has been recognized for nearly two centuries. People who have had a marked iodine deficiency and are then given high amounts of iodine as part of a preventative program are at risk of getting hyperthyroidism with clinical signs including weight loss, tachycardia, muscle weakness, and skin warmth.

Iodide, an anion, is rapidly and almost completely absorbed from the stomach and upper gastrointestinal (GI) tract. Most other forms of iodine are changed in the GI tract to iodide and completely absorbed. When thyroid hormone is ingested, about 80 percent is absorbed without change; the rest is excreted in the feces. Absorbed iodide circulates in the free form; it does not bind to proteins in blood. Iodide is rapidly removed from circulation by the thyroid and kidney. Urinary excretion is a major homeostatic mechanism. If iodine intake has been adequate, only about 10 percent of absorbed iodide appears in the thyroid, the rest appears in the urine. However, if iodine status is inadequate, a much higher percentage, up to 80 percent, can appear in the thyroid. The thyroid gland is essentially the only storage site for iodine, where it appears mostly as mono-and diiodotyrosine and T4, with a small amount of T3.

The recommended intakes of iodine for various age and sex groups are shown in Table 1, which shows that the recommended dietary allowance (RDA) for adults is 150 >g/day. Iodized salt has been the major method for assuring adequate iodine intake since the 1920s. Other sources of iodine are seafood and foods from plants grown on high-iodine soils.

Iron

This trace element is a component of molecules that transport oxygen in blood. Numerous enzymatic reactions involving oxidation and reduction (redox) use iron as the agent through which oxygen is added, hydrogen is removed, or electrons are transferred. The classes of enzymes dependent on iron for activity include the oxidoreductases, exemplified by xanthine oxidase/dehydrogenase; monooxygenases, exemplified by the amino acid oxidases and cytochrome P450; dioxygenases, exemplified by amino acid dioxygenases, lipoxygenases, peroxidases, fatty acid desaturases, and nitric oxide synthases; and miscellaneous enzymes such as aconitase.

Among the trace elements, iron has the longest and best described history. By the seventeenth century, a recognized treatment for chlorosis, or iron deficiency anemia, was drinking wine containing iron filings. Despite the extensive knowledge about its treatment and prevention, and the institution of a variety of effective interventions, iron deficiency is the primary mineral deficiency in the United States and the world today. The physiological signs of iron deficiency include anemia, glossitis (smooth atrophy of tongue surface), angular stomatitis (fissures at the angles of the mouth), koilonychia (spoon nails), blue sclera, lethargy, apathy, listlessness, and fatigue. Pathological consequences of iron deficiency include impaired thermoregulation, immune function, mental function, and physical performance; complications in pregnancy, including increased risk of premature delivery, low birth weight, and infant mortality; and possibly increased risk of osteoporosis.

Concerns have been expressed about high intakes of iron being a health issue. This has come about through epidemiologic observations associating high dietary iron or high body iron stores with cancer and coronary heart disease. Further experimental studies, however, are required to confirm whether the high intakes of iron increase the risk for these diseases. The toxic potential of iron arises from its biological importance as a redox element that accepts and donates electrons to oxygen that can result in the formation of reactive oxygen species or radicals that can damage cellular components such as fatty acids, proteins, and nucleic acids. Antioxidants are enzymes or molecules that prevent the formation of oxygen radicals or convert them to nonradical products. When not properly controlled by antioxidants, reactive oxygen damage can lead to premature cell aging and death. An iron overload disease known as hereditary hemochromatosis is caused by a defective regulation of iron transport with excessive iron absorption and high transferrin (transport form) iron in plasma. Clinical signs appear when body iron accumulates to about 10 times normal and include cirrhosis, diabetes, heart failure, arthritis, and sexual dysfunction. Hemochromatosis also increases the risk for hepatic carcinoma. The treatment for hereditary hemochromatosis is repeated phlebotomy.

Absorption from the GI tract is the primary homeostatic mechanism for iron. Dietary iron exists generally in two forms, heme and non-heme, that are absorbed by different mechanisms. Heme iron is a protoporphyrin molecule containing an atom of iron; it comes primarily from hemoglobin and myoglobin in meat, poultry, and fish. Non-heme iron is primarily inorganic iron salts provided mainly by plant-based foods, dairy products, and iron-fortified foods. Heme iron is much better absorbed and less affected by enhancers and inhibitors of absorption than non-heme iron. Iron absorption is regulated by mucosal cells of the small intestine, but the exact mechanisms in the regulation have not been established. Both iron stores and blood hemoglobin status have a major influence on the amount of dietary iron that is absorbed. Under normal conditions, men absorb about 6 percent and menstruating women absorb about 13 percent of dietary iron. However, with severe iron deficiency anemia (functionally deficient blood low in hemoglobin), absorption of non-heme iron can be as high as 50 percent. Iron loss from the body is very low, about 0.6 mg/day. This loss is primarily by excretion in the bile and, along with iron in desquamated mucosal cells, eliminated via the feces. Menstruation is a significant means through which iron is lost for women. It should be noted, however, that nonphysiological loss of iron resulting from conditions such as parasitism, diarrhea, and enteritis account for half of iron deficiency anemia globally. Excess iron in the body is stored as ferritin and hemosiderin in the liver, reticuloendothelial cells, and bone marrow.

The recommended intakes of iron for various age and sex groups are shown in Table 1, which shows that the RDA for adult males and postmenopausal women is 8 mg/day; and that for menstruating adult women is 18 mg/day. Meat is the best source of iron, but iron-fortified foods (cereals and wheat-flour products) also are significant sources.

Zinc

This trace element is the only one that is found as an essential component in enzymes from all six enzyme classes. Over 50 zinc metalloenzymes have been identified. Zinc also functions as a component of transcription factors known as zinc fingers that bind to DNA and activate the transcription of a message, and imparts stability to cell membranes.

Signs of zinc deficiency in humans were first described in the 1960s. Although it is generally thought that zinc deficiency is a significant public health concern, the extent of the problem is unclear because there is no well-established method to accurately assess the zinc status of an individual. The physiological signs of zinc deficiency include depressed growth; anorexia (loss of appetite); parakeratotic skin lesions; diarrhea; and impaired testicular development, immune function, and cognitive function. Pathological consequences of zinc deficiency include dwarfism, delayed puberty, failure to thrive (acrodermatitis enteropathica infants), impaired wound healing, and increased susceptibility to infectious disease. It has also been suggested that low zinc status increases the susceptibility to osteoporosis and to pathological changes caused by the presence of excessive reactive oxygen species or free radicals.

Zinc is a relatively nontoxic element. Excessive intakes of zinc occur only with the inappropriate intake of supplements. The major undesirable effect is an interference with copper metabolism that could lead to copper deficiency. Long-term high zinc supplementation can reduce immune function and high-density lipoprotein (HDL)-cholesterol (the "good" cholesterol). These effects are seen only with zinc intakes of 100 mg/day or more.

A primary homeostatic mechanism for zinc is absorption from the small intestine. Absorption involves a carrier-mediated component and a nonmediated diffusion component. With normal dietary intakes, zinc is absorbed mainly by the carrier-mediated mechanism. Although absorption can be modified by a number of factors, about 30 percent of dietary zinc is absorbed. The efficiency of zinc absorption is increased with low zinc intakes. The small intestine has an additional role in zinc homeostasis through regulating excretion through pancreatic and intestinal secretions. After a meal, greater than 50 percent of the zinc in the intestinal lumen is from endogenous zinc secretion. Thus, zinc homeostasis depends upon the reabsorption of a significant portion of this endogenous zinc. Intestinal conservation of endogenous zinc apparently is a major mechanism for maintaining zinc status when dietary zinc is inadequate. The urinary loss of zinc is low and generally not markedly affected by zinc intake.

The recommended intakes of zinc for various age and sex groups are shown in Table l, which shows that the RDA for adult males is 11 mg/day and for adult females is 8 mg/day. The best food sources for zinc are red meats, organ meats (for example, liver), shellfish, nuts, whole grains, and legumes. Many breakfast cereals are fortified with zinc.

Cobalt (Vitamin B12)

Ionic cobalt is not an essential nutrient for humans. Cobalt is an integral component of vitamin B12, which is an essential nutrient for nonruminant animals and humans. Vitamin B12 is a cofactor for two enzymes, methionine synthase which methylates homocysteine to form methionine, and methylmalonyl coenzyme A (CoA) mutase which converts L-methylmalonyl CoA, formed by the oxidation of odd-chain fatty acids, to succinyl CoA.

In the nineteenth century, a megaloblastic anemia (functionally deficient blood containing primitive large red blood cells) was identified that was invariably fatal and thus called pernicious anemia. The first effective treatment for this disease was 1 pound of raw liver daily. In 1948, the anti–pernicious anemia factor (vitamin B12) in liver was isolated and found to contain 4 percent cobalt. Vitamin B12 deficiency most commonly arises when there is a defect in vitamin B12 absorption caused by such factors as atrophic gastritis, Helicobacter pylori infection, and bacteria overgrowth resulting from achlorohydria and intestinal blind loops. Because vitamin B12 only comes from foods of animal origin, absolute vegetarianism will lead to deficiency in vitamin B12 after 5 to 10 years. The physiological signs of severe vitamin B12 deficiency are megaloblastic anemia, spinal cord demyelination, and peripheral neuropathy. The pathological consequences of deficiency include pernicious anemia, memory loss, dementia, an irreversible neurological disease called subacute degeneration of the spinal cord, and death. Recently, mild vitamin B12 deficiency has been cited as a cause of high circulating homocysteine, which has been associated with an increased risk for cardiovascular disease. Vitamin B12 is essentially nontoxic. Doses up to 10,000 times the minimal daily adult human requirement do not have adverse effects.

Table 1

Recommended Dietary Allowances for Selected Trace Elements Established by the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences (see bibliography).
	Recommended Dietary Allowance
	Copper (μg/day)	Iodine (μg/day)	Iron (μg/day)	Selenium (μg/day)	Vitamin B₁₂ (cobalt) (μg/day)	Zinc (μg/day)
0–6 months	—	—	—	—	—	—
7–12 months	—	—	11	—	—	3
1–3 years	340	90	7	20	0.9	3
4–8 years	440	90	10	30	1.2	5
9–13 years	700	120	8	40	1.8	8
14–18 years	890	150	11 M/15 F	55	2.4	11 M/9 F
19–50 years	900	150	8 M/18 F	55	2.4	11 M/9 F
51 years and greater	900	150	8	55	2.4	11 M/8 F
Pregnancy
18 years or less	1,000	220	27	60	2.6	13
19–50 years	1,000	220	27	60	2.6	11
Lactation
18 years and less	1,300	290	10	70	2.8	14
19–50 years	1,300	290	9	70	2.8	12
Abbreviations: F, female; M, male.

Vitamin B12 absorption is a relatively complex process. Digestion by the saliva and acid environment of the stomach releases vitamin B12 from food, then it is bound to a haptocorrin called R protein that carries it into the duodenum. A binding protein, called intrinsic factor, released by gastric parietal cells binds vitamin B12 after the stomach acid is neutralized in the duodenum, and digestive enzymes remove the R binder from the vitamin. The intrinsic factor–bound vitamin B12 is carried to a specific receptor in the ileum called cubilin and internalized by receptor-mediated endocytosis. Because vitamin B12 is water-soluble, excessive intakes are efficiently excreted in the urine.

The recommended intakes for vitamin B12 for various age and sex groups are shown in Table l, which shows that the RDA for adults is 2.4 >g/day. Food sources of vitamin B12 are of animal origin and include meats, dairy products, and eggs. Fortified cereals have also become a significant source of vitamin B12.

Copper

Copper is a cofactor for a number of oxidase enzymes including lysyl oxidase, ferroxidase (ceruloplasmin), dopamine beta-monooxygenase, tyrosinase, alpha-amidating monooxygenase, cytochrome C oxidase, and superoxide dismutase. These enzymes are involved in the stabilization of matrixes of connective tissue, oxidation of ferrous iron, synthesis of neurotransmitters, bestowal of pigment to hair and skin, assurance of immune system competence, generation of oxidative energy, and protection from reactive oxygen species. Copper also regulates the expression of some genes.

Although copper is a well-established essential trace element, its practical nutritional importance is a subject of debate. Well-established pathological consequences of copper deprivation in humans have been described primarily for premature and malnourished infants and include a hypochromic, normocytic, or macrocytic anemia; bone abnormalities resembling scurvy by showing osteoporosis, fractures of the long bones and ribs, epiphyseal separation, and fraying and cupping of the metaphyses with spur formation; increased incidence of infections; and poor growth. The consequences of the genetic disorder Menkes' disease (copper deficiency caused by a cellular defect in copper transport) in children include "kinky-type" steely hair, progressive neurological disorder, and death. Other consequences have been suggested based upon findings from epidemiological studies, and animal and short-term human copper deprivation experiments; these include impaired brain development and teratogenesis for the fetus and children, and osteoporosis, ischemic heart disease, cancer, increased susceptibility to infections, and accelerated aging for adults.

Copper toxicity is not a major health issue. The ingestion of fluids and foods contaminated with high amounts of copper can cause nausea. Because their biliary excretion pathway is immature, accumulation of toxic amounts of copper in the liver could be a risk for infants if intake is chronically high; this apparently caused cases of childhood liver cirrhosis in India.

Intestinal absorption is a primary homeostatic mechanism for copper. Copper enters epithelial cells of the small intestine by a facilitated process that involves specific copper transporters, or nonspecific divalent metal ion transporters located on the brush-border surface. Then the copper is transported to the portal circulation where it is taken up by the liver and resecreted in plasma bound to ceruloplasmin. Transport of copper from the liver into the bile is the primary route for excretion of endogenous copper. Copper of biliary origin and nonabsorbed dietary copper are eliminated from the body via the feces. Only an extremely small amount of copper is excreted in the urine. The absorption and retention of copper varies with dietary intake and status. For example, the percentages of ingested copper absorbed were 56 percent, 36 percent, and 12 percent with dietary intakes of 0.8, 1.7, and 7.5 mg/day, respectively. Moreover, tissue retention of copper is markedly increased when copper intake is low.

The recommended intakes for copper for various ages and sex groups are shown in Table 1, which shows that the RDA for adults is 900 >g/day. The best sources of copper are legumes, whole grains, nuts, organ meats (for example, liver), seafood (for example, oysters, crab), peanut butter, chocolate, mushrooms, and ready-to-eat cereals.

Selenium

Selenium is a component of enzymes that catalyze redox reactions; these enzymes include various forms of glutathione peroxidase, iodothyronine 5<-deiodinase, and thioredoxin reductase.

Although selenium was first suggested to be essential in 1957, this was not firmly established until a biochemical role was identified for selenium in 1972. The first report of human selenium deficiency appeared in 1979; the subject resided in a low-selenium area and was receiving total parenteral nutrition (TPN) after surgery. The subject and other selenium-deficient subjects on TPN exhibited bilateral muscular discomfort, muscle pain, wasting, and cardiomyopathy. Subsequently, it was discovered that Keshan disease, prevalent in certain parts of China, was prevented by selenium supplementation. Keshan disease is a multiple focal myocardial necrosis resulting in acute or chronic heart function insufficiency, heart enlargement, arrhythmia, pulmonary edema, and death. Other consequences of inadequate selenium include impaired immune function and increased susceptibility to viral infections. Selenium deficiency also can make some nonvirulent viruses become virulent.

Recently, however, not only selenium deficiency, but effects of supranutritional intakes of selenium have become of great health interest. Several supplementation trials have indicated that selenium has anticarcinogenic properties. For example, one trial with 1,312 patients supplemented with either 200 >g selenium/day or with a placebo found the selenium treatment was statistically associated with reductions in several types of cancer including colorectal and prostate cancers.

Selenium is a relatively toxic element; Intakes averaging 1.2 mg/day can induce changes in nail structure. Chronic selenium intakes over 3.2 mg/day can result in the loss of hair and nails, mottling of the teeth, lesions in the skin and nervous system, nausea, weakness, and diarrhea.

Selenium, which is biologically important as an anion, is homeostatically regulated by excretion, primarily in the urine but some also is excreted in the breath. Selenate, selenite, and selenomethionine are all highly absorbed by the GI tract; absorption percentages for these forms of selenium are commonly found to be in the 80 to 90 percent range.

The recommended intakes for selenium are shown in Table 1, which shows that the RDA for adults is 55 >g/day. Food sources of selenium are fish, eggs, and meat from animals fed abundant amounts of selenium and grains grown on high-selenium soil.

Boron

Recent findings with this trace element suggest that it may be of nutritional importance, although a clearly defined biochemical function for boron in higher animals and humans has not been defined. It has been hypothesized, however, that boron has a role in cell membrane function that influences the response to hormones, transmembrane signaling, or transmembrane movement of regulatory cations or anions. Human studies suggest that a low boron intake can impair cognitive and psychomotor function and the inflammatory response, as well as increasing the susceptibility to osteoporosis and arthritis.

About 85 percent of ingested boron is absorbed and excreted in the urine shortly after ingestion. Because boron homeostasis is regulated efficiently by urinary excretion, it is a relatively nontoxic element. A tolerable upper level intake of 20 mg/day was determined for boron by the Food and Nutrition Board of the United States National Academy of Sciences.

An analysis of both human and animal data by a World Health Group suggested that an acceptable safe range of population mean intakes for boron for adults could be 1 to 13 mg/day. Foods of plant origin, especially fruits, leafy vegetables, nuts, pulses, and legumes are rich sources of boron.

Chromium

A naturally occurring biologically active form of chromium called chromodulin has been described that apparently has a role in carbohydrate and lipid metabolism as part of a novel insulin-amplification mechanism. Chromodulin is an oligopeptide that binds four chromic ions and facilitates insulin action in converting glucose into lipids and carbon dioxide.

The nutritional importance of chromium is currently a controversial subject. Chromium deficiency has been suggested to impair glucose tolerance, which could eventually lead to diabetes. Supranutritional chromium supplementation (1,000 >g/day) has been found beneficial for some cases of type II diabetes. Supplements containing supranutritional amounts of chromium in the picolinate form have been promoted as being able to induce weight loss and to increase muscle mass. However, most ergogenic (work output) oriented studies have found chromium picolinate supplementation to be ineffective for increasing muscle mass, strength, and athletic performance, and there are no data from well-designed studies to support the claim that chromium picolinate supplementation is an effective weight loss modality. Chromium in the +3 valence state is a relatively nontoxic element.

Chromium homeostasis is regulated by intestinal absorption, which is low. Estimates of absorption range from less than 0.5 to 2 percent. Absorbed chromium is excreted in the urine.

The Food and Nutrition Board of the United States Academy of Sciences determined that there was not sufficient evidence to set an estimated average requirement of chromium. Therefore, an adequate intake was set based on estimated mean intakes. The adequate intake for young males was set at 35 >g/day, and that for young females was set at 25 >g/day. Some of the best food sources of chromium are whole grains, pulses, some vegetables (for example, broccoli and mushrooms), liver, processed meats, ready-to-eat cereals, and spices.

Conclusion

It is likely that not all the essential mineral elements for humans have been identified. Moreover, numerous biochemical functions for trace elements most likely remain to be identified. Thus, the full extent of the pathological consequences of marginal or deficient intakes of the trace elements has not been established. Furthermore, some trace elements such as selenium, fluoride, and lithium in supranutritional amounts are being found to have therapeutic or preventative value against disease. Thus, the determination of the importance of trace elements for human health and well-being should be considered a work in progress with some exciting advances likely in the future.

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Trace elements in human nutrition

Salient issues from the Joint FAO/WHO/IAEA Expert Consultation
Robert C. Weisell, Ph.D., is a Nutrition Officer in the Nutrition Planning, Assessment and Evaluation Service of the Food Policy and Nutrition Division, FAO. He is responsible for activities in nutrient and energy requirements, nutrition assessment and food composition.

In June 1990, the Joint FAO/WHO/IAEA Expert Consultation on Trace Elements in Human Nutrition was held in Geneva.1 This article draws attention to some of the important and unique aspects of the meeting. Perhaps the most notable feature was the large number (19) of nutrients discussed: iodine, zinc, selenium, copper, molybdenum, chromium, manganese, silicon, nickel, boron, vanadium, fluoride, arsenic, aluminium, lithium, tin and toxic heavy metals - lead, cadmium and mercury. Also significant was the increased attention given to the interaction between some of these nutrients. The meeting addressed the continuum of trace elements issues, from deficiencies to toxicities. Trace elements recently found to be essential were discussed,2 as were new ways of conceptualizing the application of nutrient requirements.

1 The report of this consultation will be published by the World Health Organization in 1992.
2 I the context of this consultation, an element was considered essential to an organism when reduction of exposure to it below a certain limit would result consistently in a reduction of a physiologically important function or when the element is an integral part of an organic structure with a vital function in that organism. Proof of essentiality of an element in one animal species does not prove essentiality in another, but the probability that a function is essential in any species (including the human) increases with the number of other species in which essentiality has been proved. The definitions presented are not absolute; they depend on the judgement of what constitutes a "physiologically important function" or "consistent" functional impairment, etc.

In addition, the following general subjects were discussed:

· concepts and definitions;
· trace element bioavailability;
· analytical methodology;
· trace elements in diets;
· detection and anticipation of trace element- related disorders;
· recommendations for consideration and research.
Nutrient interactions, toxicity and deficiencies

The trace elements were not examined in isolation as in the past. Instead, consideration was given to the interaction of nutrients and other components in the diet. Among the recent investigations focusing on the interaction among trace elements is the research on the essential elements selenium and iodine. There is evidence that selenium acts as a component of the enzyme responsible for converting thyroxine to triiodothyronine (T3); thus it is possible that the systemic utilization of iodine is impaired in subjects who are deficient in selenium (Arthur and Beckett, 1989; Arthur, Nicol and Beckett, 1990).

Consideration was given both to the essential trace elements and to those potentially toxic elements whose public health effects are modified by other elements. An example of this latter phenomenon is the reduced absorption of lead by a high fibre (phytate) diet. Because toxicity is covered by other units within FAO and WHO, an exploration of all aspects of toxicity was not attempted; however, reference was made to the issue.

Unlike investigations of the macronutrients (energy, protein and fat) and micronutrients (e.g. vitamin A, riboflavin), trace elements research draws on a relatively close link between the studies conducted on humans and the studies of other animals. This is because, as a general rule, trace element deficiencies elicit non-specific symptoms such as reduced growth and development; therefore when deficiencies occur they are not easily recognized. In the laboratory it is difficult to create a deficiency and, in the case of studies involving human participants, unethical. Thus research on trace elements has relied heavily upon animal studies, with attempts to relate the findings to human conditions. One example of this practice is in research on linkages between iron, copper and lead. For some time it has been recognized that iron deficiency affects the learning ability of rats and that copper deficiency and/or excessive lead intakes exacerbate the situation. Now there is increasing evidence that the same may be true in children.

Public health implications

The Expert Consultation addressed topics that are particularly relevant to an understanding of the factors governing responses to trace element deficiency or excess. The discussion extended beyond the mere levels indicating deficiency and toxicity. Subjects such as the physiological variables modifying requirements and tolerance levels were addressed, as well as topics such as bioavailability phenomena and analytical procedures. By inclusion of these issues, it was hoped that those risks related to trace element-related diseases could be identified.

Iodine, fluorine, zinc and selenium are generally thought to be essential in humans and to present substantial public health problems if deficient. Fluorine was considered essential because of its role in resistance against dental caries - was considered a physiologically important function. Even though uncomplicated selenium deficiency has not yet been demonstrated in humans, the enzyme glutathione peroxidase was considered to be a structure with a vital function and, therefore, its constituent selenium was also considered essential. Deficiencies of copper, molybdenum and chromium in humans have been described, but their importance for public health is poorly understood at present. The essential elements cobalt (in the form of vitamin B12) and iron were excluded from the consultation because they have been discussed in an FAO/WHO publication (FAO/WHO, 1988).

Cadmium, lead and mercury are of primary concern as contaminants; the danger of overexposure and excessive concentrations of these elements occurs in food chains in many parts of the world. They have been studied intensively, and the results of these studies and recommendations of safe intakes are documented in several WHO publications (WHO 1989a, 1989b, 1989c, 1990). For this reason they were treated only briefly.

New trace elements

Boron, chromium, manganese, nickel, tin, vanadium, molybdenum, arsenic, lithium, aluminium, strontium, cesium and silicon are regarded as new trace elements in the sense that they have only recently been considered essential in human diets. These elements are the subject of exciting research in animals, particularly ruminants, where they have been shown to be essential in one or more species. For example, ruminants feeding on grass grown in soil where molybdenum levels are abnormally high have demonstrated an increased tendency to exhibit copper deficiency. However, for many of these new trace elements, such as manganese, there is no evidence at the present time that abnormally low or high dietary intakes cause substantial nutritional problems in human populations.

PREPARING FOR THE CONSULTATION

The process of preparing for the consultation was itself unique. In earlier expert-consultations, 12 to 20 experts in various aspects of the subject were invited to prepare background papers and to attend the expert committee or consultation1 in their individual capacity. Normally there was no meeting prior to the committee meeting or consultation itself. In contrast, the preparation for the 1990 consultation entailed a series of preliminary gatherings at which the specific problems could be dealt with by those expert in that field and a solution sought.

1 One of the earliest and continuing activities of FAO has been determining the requirement level for energy and selected macro-and micronutrients. Normally, the review process was accomplished through a standing Expert Committee, a body established by the FAO Conference on a periodic basis, but later reliance rested with the less formal Expert Consultation. The first Committee on Calorie Requirements was sponsored solely by FAO but, very soon, FAO and WHO undertook the review process jointly, initiating what has become a successful and cordial partnership. The decision to conduct an expert committee or expert consultation on a particular nutrient or group of nutrients is usually based on the perceived need, both in terms of the new scientific information available for consideration and in terms of the public health problems associated with the nutrient or nutrients. Normally one consultation is held in a biennium.

Regarding this particular expert consultation, in August 1988 the three organizations convened an expert advisory group with the charge of considering the content and format of the report and recommending an action plan for its implementation. That group included five scientists from both developing and developed countries and a representative of the secretariat. The group agreed on the contents and the organization of the consultation and its report and proposed coordinators who would be responsible for individual chapters while drawing upon inputs from solicited contributors. It was recognized that the value of the final document would depend on the applicability of its recommendations to a large variety of nutritional situations and cultures; thus contributions from scientists of many different backgrounds were needed.

For most of the chapters communication between contributors and coordinators was by correspondence, but for the chapters on copper, zinc and selenium personal contact was considered necessary. For these elements small workshops were convened in Washington, D.C., consisting of four to six experts who not only Contributed important original data, but also represented different philosophies in their interpretation.

A subsequent informal gathering of the Expert Advisory Group and most of the coordinators was held in August 1989 in Tokyo, taking advantage of the meeting of the International Society on Trace Element Research in Humans. The consensus reached at this informal meeting, findings of the workshops and contributions by correspondence were incorporated into the draft chapters, which were examined and discussed at a meeting of the Expert Advisory Group and coordinators of most the chapters in Geneva in October 1989. The participants agreed on content, style and format and on a timetable for submission of the revised drafts, and recommended an editor to consolidate the chapters.

The Expert Consultation itself consisted of 18 participants and six representatives of the WHO, FAO and IAEA secretariats who met in Geneva in June 1990 to discuss and approve the form and content of the chapters.

Varying knowledge for particular elements

Because of the vast differences in knowledge of dietary intakes, metabolism and requirements, the quality of the data bases upon which the final decisions regarding requirements must be made varies substantially among the individual elements. For example, there is an impressive amount of data relating different levels of intake to deficiency, adequacy and toxicity of selenium. In contrast, there is only indirect and often fragmentary evidence for other trace elements. Homeostasis of different elements is maintained by different means, and the mechanisms regulating absorption of excretion in response to changes in nutritional status are poorly quantified. Yet these mechanisms, together with hundreds of dietary interactions affecting biological availability, have a profound effect on dietary requirements. Whenever the experts lacked exact data to make a strict statistical derivation of requirements, common sense and consensus after extensive discussion produced a final recommendation.

Concepts and definitions

Considerable attention was devoted to definitions (e.g. essentiality) and the conceptual framework of requirements. Although the definitions and concepts were not identical to those used in previous expert consultations (FAO/WHO, 1973, 1988; FAO/WHO/UNU, 1985), there was a logical extension of the thinking and rationale underlying the earlier reports. It was difficult to develop and assimilate some concepts; this occurred most often with the "minor" trace elements for which there was a lack of data. In addition, information for applying the concepts was not always available for some nutrients.

Recommendations for populations

In the report, the recommendations are presented in the form of safe ranges of intake for population groups, wherever the available data permit. These ranges do not represent individual requirements but describe the limits of adequacy and safety of the mean intake of whole populations. If the population mean intake falls within these limits, practically all members of that population are considered to have an adequate intake. An understanding of the conceptual framework of the recommendations is imperative to the application of the recommendations.

The practical applications and limitations of the information on dietary content and availability of the trace elements were considered. When possible, recommendations were made for acceptable lower and upper limits of mean population intakes. There were some surprising conclusions; for example, the recommended range for chromium was reduced by a factor of several hundred, primarily because of extreme measurement errors in the older laboratory techniques.

The final part of the report presents the recommendations of the experts for future activities. A few recommendations relate to research approaches needed to fill important gaps in our knowledge and in our ability to diagnose marginal states of trace element nutrition. The intention of the remaining recommendations is to increase awareness of the great potential health benefits of intervention programmes for whole populations in which trace element deficiencies, environmental or dietary, have been diagnosed. The conquest of iodine deficiency disorders in many countries (Hetzel, 1988) and of Keshan disease in China (Keshan Disease Research Group, 1979) are cited as examples of what can be achieved.

REFERENCES

Arthur, J.R. & Beckett, G.J. 1989. Selenium deficiency and thyroid hormone metabolism. In A. Wendel, ed. Selenium in biology and medicine, p. 90-95. Berlin, Springer.

Arthur, J.R., Nicol, F. & Beckett, G.J. 1990. Hepatic iodothyronine 5' deiodinase: the role of selenium. Biochem. J., 272 (2): 537-540.

FAO/WHO. 1973. Energy and protein requirements, Report of a Joint FAO/WHO Ad Hoc Expert Committee. FAO Nutr. Meet, Rep. Ser. No. 52; WHO Tech. Rep. Ser. No. 522, Rome, FAO/Geneva, WHO.

FAO/WHO. 1988. Requirements of vitamin A, iron, folate and vitamin B12. Report of a Joint FAO/WHO Expert Consultation. FAO Food Nutr. Ser. No. 23, Rome, FAO.

FAO/WHO/UNU. 1985. Energy and protein requirements. Report of a Joint FAO/WHO/UNU Expert Consultation. WHO Tech. Rep. Ser. No. 724. Geneva, WHO.

Hetzel, B.S. 1988, Iodine deficiency disorders, Lancet, 1988 (1): 1386-1387.

Keshan Disease Research Group. 1979. Observations on effect of sodium selenite in prevention of Keshan disease. Chin. Med. J., 92: 471-476.

WHO. 1989a. Environmental health criteria 85: lead. Geneva, WHO.

WHO. 1989b. Environmental health criteria 86: mercury-environmental aspects. Geneva, WHO.

WHO. 1989c. Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Ser. No. 24. Geneva, WHO.

WHO. 1990. Environmental health criteria 101: methylmercury. Geneva, WHO.

Les éléments-traces dans la nutrition humaine
Cet article passe en revue les principaux points mis en relief par la Consultation d'experts FAO/OMS/AIEA sur les éléments-traces dans la nutrition humaine, la plus récente d'une série de consultations sur les besoins énergétiques et nutritifs dont la première eut lieu juste après la fondation de la FAO. Il contient également une description des préparatifs et des travaux eux-mêmes, qui ont culminé avec la tenue de la Consultation à Genève du 18 au 22 juin 1990.

Cette consultation a revêtu une importance exceptionnelle compte tenu du grand nombre d'éléments nutritifs examinés (19) et de leur grande diversité du point de vue de leur importance, de leur caractère essentiel sur le plan nutritionnel, de leur fonction et de leur importance pour la santé publique. Pour chaque élément nutritif, la Consultation a examiné, selon le cas, le spectre complet carence-toxicité, présenté dans un cadre conceptuel qui a évolué au cours des 15 dernières années et que l'article du professeur Beaton décrit plus en détail (voir pages 3 à 15 de ce numéro). La tendance, Jadis, consistait à examiner les éléments nutritifs isolément mais, dans le cas des éléments-traces, une attention spéciale était réservée aux interactions entre éléments nutritifs d'une part et les autres éléments constitutifs du régime alimentaire d'autre part.

Etant donné les différences d'importance et d'essentialité, les niveaux recommandés n'étaient pas toujours pertinents. Toutefois, lorsqu'on disposait de données sur leur teneur dans le régime alimentaire et que leur rôle biologique précis avait été défini, des limites supérieures et inférieures ont été recommandées concernant les doses moyennes d'absorption d'une population.

Un autre aspect particulier de la Consultation a été la succession de faits qui a conduit à la réunion elle-même. Normalement, un certain nombre de documents de travail sont rédigés par des experts qui sont censés assister à la Consultation. Il n'y a cependant pas de réunions préparatoires. Dans le cas présent, des groupes d'experts ont travaillé en collaboration sur chaque élément nutritif, groupe d'éléments nutritifs ou aspects importants des éléments-traces. Ces groupes ont rédigé les chapitres les concernant respectivement; ces chapitres ont ensuite été examinés par un Groupe consultatif d'experts à plusieurs reprises pendant la période de préparation et, pour finir, ont été soumis à l'examen de la Consultation elle-même.

Los oligoelementos en la nutrición humana
En este artículo se examinan los principales aspectos abordados por la Consulta FAO/OMS/OIEA de Expertos sobre los Oligoelementos en la Nutrición Humana, la más reciente de una serie de consultas sobre las necesidades de energía y nutrientes iniciada inmediatamente después del establecimiento de la FAO. También se hace una breve descripción de los preparativos y el proceso que culminaron en la celebración de la Consulta en Ginebra del 18 al 22 de junio de 1990.

La Consulta fue extraordinaria por el gran número de nutrientes examinados (19) y por su amplia diversidad en cuanto a importancia, carácter nutricional esencial, función y significación desde el punto de vista de la salud pública. Se estudió todo el espectro de deficiencia-toxicidad de cada nutriente, cuando procedía, y las conclusiones se presentaron en un marco conceptual elaborado durante los últimos 15 años, examinado en forma más detallada en el artículo del Prof. Beatón. Tradicionalmente se ha registrado una tendencia a abordar los nutrientes por separado, pero en el caso de los oligoelementos se prestó especial atención a la interacción de los nutrientes y los demás componentes de la dieta.

A causa de la diversidad en cuanto a importancia y esencialidad, los niveles recomendados no siempre fueron relevantes. Sin embargo, cuando se disponía de información sobre el contenido dietético y se había definido una función biológica precisa, se formularon recomendaciones en relación con los límites inferior y superior de las ingestas medias de la población.

Otro aspecto de la Consulta único en su género fue la serie de acontecimientos que dieron lugar a la reunión propiamente dicha. Normalmente los distintos expertos cuya asistencia se prevé preparan varios documentos de trabajo; sin embargo, no se celebran reuniones preliminares. En el caso presente, varios grupos de expertos trabajaron en colaboración con respecto a cada nutriente, grupo de nutrientes o algún aspecto importante de los oligoelementos. Esos grupos redactaron los capítulos respectivos que después fueron examinados varias veces por un grupo asesor de expertos durante el periodo preparatorio y, por último, se presentaron a la Consulta para su debate.

Article Source:

http://www.fao.org/docrep/u5900t/u5900t05.htm

A Partial List of the 72+ Trace Elements in Seafood

Our daily food, as produced by our modern agriculture, contains:

►3 - major nutrients (nitrogen, phosphorus and potassium - or N-P-K);

►6 - minor nutrients (calcium, chloride, magnesium, iron, sodium, sulphur) and

►5 - trace elements as monitored and maintained in agricultural soils
(boron, copper, manganese, molybdenum, zinc) and

3 - trace elements as added at other stages of our nutrition
(iodine in table salt; cobalt in salt licks for cattle and sheep; and selenium in fortified chicken feed)
- for a total of 8 (!) nutritional trace elements.

All of the above vital nutrients are generally available in adequate amounts in today's agriculturally grown food products. However, since cobalt and selenium are added to livestock feed, rather than to the soil, pure vegetarians are at some risk of cobalt and selenium deficiencies.

However, all living things need about 72 (!) biological trace elements - as found throughout nature and in all 'wild' plant and animal life - for the normal function of their metabolism, reproductive and immune systems. Today, the only readily available food which still contains the complete natural range of the 72 biological trace elements is seafood.

Further, and although the trace element zinc is routinely monitored and maintained in agricultural soils, there are very strong indications (a sharp rise of birth defects in new-borns) that we do not get enough zinc in our daily food.

Trace elements - also called trace minerals - occur in the soil, and are needed for the normal function of all plant and animal metabolic, reproductive and immune systems in miniscule traces; hence the name trace elements. One part per million, and often less, is typical of the amounts needed.

Although far from complete, the following is the most extensive list of biological trace elements as found in a representative cross-section of seafood, which I have been able to find. They are listed here in their amounts (in parts per million), their status of recognition by the biomedical and agricultural sciences, and their availability in our agriculturally produced food.

Note - Dec. 1998: Very recent research indicates that we need somewhere around 72 trace elements for our health and well being - and surprisingly, even micro-miniscule traces of the 'heavy' elements, among them lead, mercury, cadmium, asf. However, we are getting far too much of the heavy metals already through industrial and chemical pollution.

Article Source:

http://www.truehealth.org/atrclist.html

Trace elements detection overview

Trace elements are chemicals that are required by organisms in very small quantities for proper physiological and biochemical functioning. Trace elements commonly occur in organisms in concentrations smaller than about 0.001% of the dry weight (less than 10 parts per million, or ppm). Listed in alphabetical order, the most commonly required trace elements for healthy animal or plant nutrition are: boron (B), chlorine (Cl), chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), silicon (Si), tin (Sn), vanadium (V), and zinc (Zn). Some organisms also appear to require aluminum (Al) and nickel (Ni).

All of the 92 naturally occurring elements occur ubiquitously in the environment, in at least trace concentrations. In other words, there is a universal contamination of soil, water, air, and biota with all of the natural elements. As long as the methodology of analytical chemistry has detection limits that are small enough, this contamination will always be demonstrable. However, the mere presence of an element in organisms does not mean that it is indispensable for healthy biological functioning. To be considered an essential element, three criteria must be satisfied: (1) the element must be demonstrated as essential to normal development and physiology in several species, (2) the element must not be replaceable in this role by another element, and (3) the beneficial function of the element must be through a direct physiological role, and not related to correction of a deficiency of some other element or indirect correction of a toxic condition.

Research into the physiological roles of trace elements is very difficult, because it involves growing plants or animals under conditions in which the chemical concentrations of food and water are regulated within extremely strict standards, particularly for the trace element in question. In such research, even the slightest contamination of food with the trace element being examined could invalidate the studies. Because of the difficulties of this sort of research, the specific physiological functions of some trace elements are not known. However, it has been demonstrated that most trace elements are required for the synthesis of particular enzymes, or as co-fators that allow the proper functioning of specific enzyme systems.

A principle of toxicology is that all chemicals are potentially toxic. All that is required to cause toxicity is that organisms are exposed to a sufficiently large dose. The physiological effect of any particular dose of a chemical is related to the specific susceptibility of an organism or species, as well as to environmental conditions that influence toxicity. This principle suggests that, although trace elements are essential micronutrients, which benefit organisms that are exposed within certain therapeutic ranges, at larger doses they may cause biological damages. There are many cases of biological and ecological damages being caused by both naturally occurring and human caused pollutions with trace elements. Such occurrences may involve the natural, surface occurrences or metal-rich minerals such as ore bodies, or emissions associated with certain industries, such as metal smelting or refining.

Article Source:

http://science.jrank.org/pages/6890/Trace-Elements.html

Minerals and Trace Element Research

In recent years, many spectacular and far-reaching advances in the knowledge and role of minerals and trace elements in human health and disease have been made. Several new trace elements have been discovered and analytical techniques to measure trace elements have grown in their sophistication. Nineteen minerals are considered significant for human health. Some of these are essential for growth and development such as iron, zinc and iodine. Others are essential but we know less about their exact requirements such as copper and manganese. Finally, some are not only essential but can also be associated with adverse effects at high intakes, for example, selenium or calcium.

Minerals are unique nutrients because they are extremely active metabolically, and can be both potent intracellular oxidants through their role as mineral catalysts as well as antioxidants through their role as an essential part of many important enzymes. Minerals are subject to numerous interactions with other components in the diet, such as fat and protein and vitamins C and E and with each other. Since new evidence concerning the benefits of trace elements and risks associated with mineral deficiencies and interactions are continually emerging, a number of studies are conducted at Health Canada to address these questions.

The research is used in numerous areas of nutritional policy setting in the Food Program, such as review of the policies concerning the addition of vitamins and minerals to foods, standard setting activities such as establishing mineral levels for infant formulas, and determining the safety and effects of food processing or changes in food composition on mineral levels and requirements and is used in many risk assessments conducted in the Department.

Article Source:

http://www.hc-sc.gc.ca/fn-an/res-rech/res-prog/nutri/micro/minerals_trace_element_research-recherche_minerals_oligoelement-eng.php

Impact of Trace Elements

Background Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables.

Objective To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people.

Methods This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2x2 factorial design for 2 years.

Main Outcome Measures Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality.

Results Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P=.06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups.

Conclusions Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.

INTRODUCTION
Jump to Section
• Top
• Introduction
• Patients and methods
• Results
• Comment
• Author information
• References

IT IS well known that aging is often associated with a poor immune response, particularly the cell-mediated response,1 and substantial vulnerability to respiratory tract infections. The latter are significant causes of morbidity and mortality in the elderly, particularly those with chronic diseases.2

Nutritional status has been recognized as a strong factor in immune impairment, especially in elderly persons in institutions.3 Moreover, there is a high incidence of malnutrition among long-term nursing home residents because of inadequate intake of several nutrients,4 which increases impairment of natural immunity.

It has been shown that in this population, supplementation with different nutrients enhances immune status, such as the delayed-type hypersensivity skin response,5 the proliferative response to mitogens,6 and natural killer cells,7 and the antibody response to vaccine.8-9 Nevertheless, in a few studies,10-13 immunologic responses were found to be impaired with large quantities of nutrients. In addition, results of a recent study14 demonstrate an improvement in immunity and a decrease in the incidence of infections after supplementation with low doses of micronutrients.

This trial was performed within a large multicentric study to determine the effects of long-term daily supplementation with trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people.

PATIENTS

A total of 725 long-term institutionalized elderly patients (185 men and 540 women) with a mean age of 83.9 years (age range, 65-103 years) were recruited in 25 nursing homes throughout France between April 1992 and April 1993 (Figure 1). A medical history was obtained for each patient before enrollment. They had no acute illness and were at least 65 years of age but often required long-term care because of age-related diseases (osteoarthritis, hypertension, residual stroke, etc). Patients with a history of cancer or those taking medication that might interfere with nutritional status, immunocompetence, or vitamin or mineral supplements were excluded.

PROTOCOL

The study had a double-blind, placebo-controlled, 2x2 factorial design. Elderly patients were stratified by sex and age and randomly assigned to 1 of 4 treatment groups using block randomization in each geriatric center. Patients received 1 capsule daily, with their breakfast, for 2 years. The capsule contained 1 of the 4 following preparations: (1) zinc sulfate and selenium sulfide (providing 20 mg of zinc and 100 µg of selenium)—the trace element (T) group; (2) ascorbic acid (120 mg), beta carotene (6 mg=1000 retinol equivalents), and -tocopherol (15 mg)—the vitamin (V) group; (3) trace element and vitamin supplements—the vitamin and trace element (VT) group; or (4) placebo (calcium phosphate and microcrystalline cellulose)—the placebo (P) group.

Supplements and placebo were provided in capsules of identical aspect and were prepared specifically for this study (Produits Roche SA, Fontenay-aux-Roses, France). The capsules were given to the geriatric centers in individual pill boxes every 6 months.

Levels of nutrients used in this study were nutritional doses, lower than or equal to 2-fold the French and US recommended daily allowances.

Compliance was verified first by the nursing teams that administered the pills every morning and then at the end of each 6 months by counting the remaining capsules in the pill boxes. Another way of assessing compliance was to examine the course of blood micronutrient concentrations.

Twenty-five milliliters of whole blood was withdrawn from each fasting patient by venipuncture between 7:00 and 8:00 AM at study inclusion and after 6 and 12 months of supplementation for the whole population for blood nutrient determinations. In 4 centers (135 patients), another blood sample was taken at the end of the trial.

BIOCHEMICAL MEASUREMENTS

Biological factor determinations have been described in detail elsewhere.15 Low levels of nutrients were defined according to results from the literature.16-17

IMMUNE FACTORS

At baseline and after 6 and 12 months of supplementation, delayed-type hypersensitivity skin test responses to 7 antigens were assessed in a representative subsample of 173 elderly people using the Merieux Multitest applicator (Pasteur-Merieux, Lyon, France). The antigens were tetanus toxoid antigen, diphtheria toxoid antigen, streptococcus antigen, tuberculin, Candida albicans antigen, Proteus mirabilis antigen, and Trichophyton mentagrophytes antigen. Glycerine was used as a control injection. All skin tests were administered and the results read by the same investigator (F.G.), who did not know the type of supplement for each patient. Skin reactions were assessed 48 hours after injection by measuring mean induration diameter. Only indurations larger than 2 mm were considered positive. For each patient, we reported the number of positive responses and total sum of induration sizes in millimeters (indurations <2 mm were not counted in the sum of induration sizes).

Purified split virion vaccine containing a strain of influenza virus (A/ Singapore/6/86 (H1N1)-like, A/Beijing/32/92(H3N2)-like, and B/Panama/45/90-like) was injected into a representative subsample of 140 patients after 15 to 17 months of supplementation. Serum samples were frozen and stored at -20°C. Antibody titers against the vaccinal strain were assessed by a standard hemagglutination inhibition test18 before injection of the vaccine and after 28, 90, 180, and 270 days. Titers of less than 9 were arbitrarily coded as 5. An antibody titer of 80 or greater was unequivocally considered to be a protective titer.

CLINICAL STUDIES

In each nursing home, a diagnosis of infectious events was made by the same physician. We considered an infection as urologic when it was symptomatic and associated with more than 1x106/mL of the same bacteria and more than 1x105/mL leukocytes in urine. Respiratory tract infections were based on clinical symptoms (cough, fever, and purulent sputum) and radiological test results. Only respiratory tract and urogenital infections were recorded because they are well standardized, frequent, and often severe in this population.

STATISTICAL ANALYSIS

Statistical analyses were performed on an intention-to-treat basis on all randomized patients using the SAS software program.19 Mean comparisons were determined by 2-way analysis of variance testing for a trace element effect, a vitamin effect, and a trace element–vitamin interaction. Statistical significance was based on P<.05. Validity of the assumptions was checked by a normal probability plot of residuals and the Bartlett F test of homogeneity of variances. When normal distribution was not obtained, logarithmic transformation was used to improve normality and stabilize variances.

The impact of supplementation on infectious incidence was assessed using logistic regression after grouping infectious events that occurred during follow-up into 4 groups: no infection and 1, 2, and 3 or more infectious events.

COMMENT
Jump to Section
• Top
• Introduction
• Patients and methods
• Results
• Comment
• Author information
• References

Few such trials of vitamin–trace element supplementation in elderly patients have been carried out, and most have been of limited size. Patients were stratified by sex and age and randomly assigned to 1 of 4 treatment groups using block randomization in each geriatric center to avoid selection bias. Study duration was 24 months to exclude seasonal variation in infectious morbidity. Moreover, clinical benefits were evaluated in addition to biological factors. Finally, doses of nutrients used were moderate, compared with previous studies that reported adverse effects with use of large doses.12-13

Dietary intakes were not assessed by food records. However, results of a previous epidemiological study20 show that the serum values of antioxidant nutrients closely correlated with intakes.

In our study, supplementation with low doses of nutrients improved serum concentrations, with good efficiency at reducing the proportion of patients with low initial levels. Except for zinc, the serum concentration reached a plateau after 6 months. For zinc, the serum concentration increased slowly during the study. It is well known that zinc has low intestinal absorption, especially in the elderly.21 In elderly patients receiving supplementation for 1 year, Bogden et al13 described an increase in plasma zinc concentration in the group receiving 100 mg/d but no change in the group receiving 15 mg/d. As in other studies6, 22 in elderly patients, selenium supplementation induced an increase in the level of serum selenium. In the same way, a significant improvement was also effected in serum vitamin values, which confirmed previously published results.5

High compliance (>85%) was observed, as confirmed by the increase in serum nutrient values in the treated groups and no changes in the P group.

Regarding delayed-type hypersensitivity responses, we observed a decrease in the number of positive responses and the sum of induration sizes in all groups with time; supplementation was unable to limit this decrease in cellular immunity. Our results contrast with others,5 in which an improvement in delayed-type hypersensitivity was reported after low-dose multivitamin-mineral (24 different nutrients) supplementation. This difference may be caused, in part, by the composition of supplements and populations studied elsewhere, in which delayed-type hypersensivity was enhanced after supplement use in apparently healthy and independently living younger patients.

The antibody response on days 28 and 90 after influenza vaccine was improved in the T groups (alone or associated with vitamins) in a 2x2 factorial analysis of variance. In the same way, there were more serologically protected patients in the T groups than in the non-T groups (P=.04).

Our results suggest that zinc and selenium supplementation improves the humoral response after influenza vaccine in elderly people. It has been shown that supplementation with the same dose of zinc (20 mg/d) leads to a significant restoration of serum thymulin activity in elderly patients.23 This thymic hormone requires the presence of zinc to express its biological activity and is involved in thymocyte proliferation. The antibody response to influenza vaccine is T-lymphocyte dependent, suggesting that more effective thymulin activity could induce a better anti-influenza response.

Moreover, it is well known that protein-energy malnutrition induces a weak immune response, whereas nutritional supplementation is effective in restoring responses to vaccines.24 In a previous study, Chandra and Puri8 recruited 30 elderly people who had nutritional deficiencies: 15 received supplements and 15 did not. An improvement in antibody response to the influenza vaccination was noted in patients taking supplements after oral dietary and medicinal supplementation appropriate for the type of malnutrition.8 Boukaïba et al23 described an enhancement of food intake and serum albumin level after 8-week supplementation with zinc in hospitalized elderly patients. This type of zinc supplementation might increase nutritional status and secondary immune functions.

Vitamin supplementation was associated with a weaker humoral response. Our results agree with those of a previous trial25 that studied the impact of 200- and 400-mg vitamin E supplementation on humoral response after influenza vaccine in 103 men. No benefit of vitamin E was observed in terms of serum titers or the incidence of pulmonary, urinary tract, or other infections in that study, in which 75% of the patients were older than 69 years.

In the subsample of 140 vaccinated patients, no significant reduction in respiratory tract infections clearly appeared (P>.10) during the 7 months after the influenza vaccine, but there were only 31 respiratory tract infections and we probably lacked power to observe a reduction in infectious morbidity during such a short time.

Fewer respiratory tract infections were found in patients who received trace elements, whereas no reduction in urogenital infections was noted during the 2-year supplementation. Nevertheless, logistic regression analysis after pooling the infections into 4 classes (0, 1, 2, and 3) showed no benefit of trace element supplementation in respiratory tract infections. This discrepancy between the 2 methods used to explore respiratory tract infections might be explained by the higher rate of repeated infections in the VT group (Table 6). There were 3 patients in the T and VT groups and only 1 patient in the P and V groups with more than 4 infections.

Previous 4-month multivitamin supplementation of healthy elderly patients did not show any protection against infection, but the duration was probably too short.26 Another trial14 with 96 healthy elderly patients living independently for 1 year found a significant decrease in infection-related illness that correlated with an improvement in immunologic responses. The supplement contained 11 vitamins and 7 trace elements ranging from 50% to 200% of the recommended dietary allowances. It was the only large-scale study that showed the clinical benefits of multinutrients on infections. Nevertheless, the results concerned the duration of infectious events and not their incidence. In our study, we preferred to express the infectious events as new cases because we believe that, although it is easy to determine the beginning of an infection, it is more difficult to determine exactly when it ends (the day of fever, day of arrest of symptoms, or day of normalization of the C-reactive protein or leukocytes).

Concerning the use of a single nutrient, results of recent studies27-28 demonstrate the role of modest doses of zinc (10-20 mg/d) in reducing the occurrence of diarrhea in children, but zinc supplementation did not decrease the incidence of respiratory tract infections. Only 1 trial performed on children with Down syndrome who received 1 mg of zinc per 1 kg of body weight per day showed a reduction in respiratory tract infections, but this effect was restricted to boys (n=12), and the duration of supplementation was only 4 months.29

Likewise, supplementation with low doses of selenium has been demonstrated to improve immune factors in the elderly,8 but their clinical impact remains to be studied.

No effect on mortality of any treatment, alone or in association, was observed in our trial. Nevertheless, our results agree with those of other intervention trials. The benefits of such supplementations in terms of mortality are controversial. In the Linxian trials,30 in which nearly 30,000 patients randomly received low doses of micronutrients for 5.25 years, a combination of beta carotene (15 mg), vitamin E (30 mg), and selenium (50 µg) induced a reduction in cancer risk and, consequently, a reduction in mortality rate. Nevertheless, the patients were younger (40-69 years) and inhabitants of the Linxian region in China, which has one of the world's highest rates of gastric cancer.30

Results of recent studies indicate that vitamin E supplementation may be helpful in the prevention of new heart attacks in patients with coronary disease,31 as selenium supplementation was in patients with skin cancer.32 However, no benefit of beta carotene (20 mg) or vitamin E (50 mg) in terms of cancer mortality was observed in 29,133 male smokers after 5 to 8 years of supplementation33 or in physicians given long-term antioxidant vitamin supplementation,34 and daily nutritional supplementation did not increase longevity in users of trace elements and vitamin supplements.35

In conclusion, long-term institutionalized elderly people have moderate vitamin and/or trace element biological deficiencies, which are corrected by nutritional dose supplementation with adequate micronutrients. In our study, patients who received zinc and selenium had a better antibody response after influenza vaccine, and the percentage of patients without respiratory tract infections was higher in the T and VT groups. Our results suggest a beneficial effect of these nutrients on the immunity of elderly persons by improving their resistance to infections. Larger trials will be required to confirm our findings, which may have considerable impact on the health of the institutionalized elderly.

Article Source:

http://archinte.ama-assn.org/cgi/content/full/159/7/748

Trace Elements and Supplement

The inhabitants of almost any saltwater aquarium require supplements added to the water. The type of supplements depends upon the type of inhabitants, as shown in the following table. The trace elements of special concern for reef tanks include calcium, iodine, and strontium.

Marine Aquarium Containing:	Supplement	Benefit
Small or Large Polyp Stony Corals, Giant Clams, Leather Corals, Polyps, Mushroom Anemones	Calcium	Helps build skeleton
	Iodine	Helps prevent damage due to excessive light exposure
	Strontium	Helps build skeleton
	Magnesium	Helps prevent premature calcium precipitation
	Buffer (Alkalinity)	Helps build skeleton; buffers pH
	Trace Element	Helps facilitate enzymatic and photosynthetic reactions
	Plankton Suspension	Provides nutrients that are not produced by the target organism
	Vitamin	Helps maintain health, color, and facilitates biological reactions

Crustaceans and other Motile Invertebrates	Calcium	Helps build skeleton
	Magnesium	Helps prevent premature calcium precipitation
	Iodine	A component of the animal's exoskeleton; aids in the molting process
	Buffer (Alkalinity)	Buffers pH
	Trace Element	Helps facilitate enzymatic reactions
	Vitamin	Helps maintain health, color, and facilitates biological reactions

Fish-Only	Iodine	Helps prevent health disorders such as goiter
	Buffer (Alkalinity)	Buffers pH
	Trace Element	Helps facilitate enzymatic reactions
	Vitamin	Helps maintain health, color, and facilitates biological reactions

Replenishing trace elements

Over the course of time, many of the "trace" elements in reef aquarium water become depleted. Several processes are responsible for this depletion. Protein skimming can trap some trace elements with the removed organics and protein. The use of Granulated Activated Carbon (G.A.C.) or other chemical media adsorbs or absorbs some trace elements. Materials of the reef system, like hosing, glass, etc., also adsorb and remove some trace elements. Most importantly, growth of the reef inhabitants reduces the available supply of trace elements.

You can replenishment depleted trace elements in several ways: through feeding, water changes, and liquid supplements.

Whenever you feed your reef, some trace elements are contained in the foods and are used by the creatures digesting the foods. In most reef systems, feeding is done very sparingly to avoid a build-up of waste products. Some hobbyists take this to the extreme and end up with anorexic fish. Please be sure to provide enough food for the proper health of your fish. (Nitrate build-up can be controlled with any number of easy-to-use products.)

All quality salt mixes include the trace elements required by corals, fish, and invertebrates. Monthly water changes of 20% to 30% are recommended to replenish any elements which may have been exhausted.

In a heavily-stocked reef aquarium, elements are often depleted at a much faster rate, and should be replenished by using commercially available reef supplements. It is best to use the appropriate test kits to monitor the levels of these important trace elements.

Calcium requirements and supplementation

Possibly the most important trace element to be kept at proper levels is calcium, which should ideally be maintained at 350 to 450 PPM. While these levels are far from "trace" levels, depletion of this element is rapid; constant monitoring is required to maintain proper levels. Proper levels of calcium help maintain the carbonate pH buffer system and cause excess phosphate to precipitate, while providing a necessary element for coral skeletal growth.

There are several options to replenish the calcium. The most popular method involves dosing the reef aquarium every day with a mixture of lime water (Kalkwasser). Caution must be used to add the Kalkwasser slowly, as a sudden increase can cause a precipitation of magnesium carbonate and can also deplete the pH buffering system, allowing a sudden increase in pH.

A second method to supply the correct level of calcium is to use calcium chloride and a buffer. This method is simple, but it is difficult to stabilize the calcium and buffer levels and can result in unacceptable fluctuations. Tanks with only small amounts of coralline algae and a small population of soft corals could be adequately maintained by this method.

Balanced supplements are available and are easy to use once appropriate levels of calcium and alkalinity have been acheived. These supplements are more expensive and may be cost prohibitive for large tanks with SPS corals.

The last method available to dose calcium involves the use of a calcium reactor with CO2 injection. These reactors are filled with calcium carbonate; a circulation pump within the reactor mixes the saltwater and CO2 to produce a pH of approximately 6.5, allowing the calcium to dissolve into the saltwater. The rate of water discharged from the reactor is several drops per minute and can be controlled by a valve. These systems can be automated with a pH controller and magnetic valve, allowing you to leave the system alone for several weeks, while you take a much needed vacation. These units require close monitoring and the initial cost of the reactor and CO2 system is comparatively high.

Liquid supplements to maintain other trace elements

Addition of the remaining trace elements is best accomplished with the use of liquid supplements. Trace elements can be overdosed into the aquarium, so be careful and monitor these levels with the appropriate test kit and keep and eye on the overall health of the aquarium.

Usually, iodine/iodide is offered by itself, and is important for increased soft coral growth and carapace production in shrimp and crabs. Iodine is depleted by protein skimming and should be kept at 0.06 PPM, although being careful not to overdose.

Strontium is utilized by both hard corals and invertebrates and should be maintained at a level of 8 ppm with the use of a liquid supplement.

Barium (used in coral skeleton growth) and iron (required by the photosynthetic zooxanthellae and macroalgae), are usually available in a trace element supplement. Several of these products are available, and, of course, everyone has their favorites. It is probably best to try several to see which family of supplements gives you the best results. Many reef keepers advocate the addition of molybdenum, though any improvement is the result of improved bacterial (nitrifying and denitrifying) action versus any direct effect on the corals.

Article Source:

http://www.peteducation.com/article.cfm?c=16+2167&aid=2386

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