Hair as a biopsy material: trace element data on one man over two decades.

BACKGROUND: Hair mineral analyses are being performed frequently both with and without medical advice. Reasons for analysis often are ill defined. OBJECTIVE: To assess variability of trace element data both within a series of samples from an individual and among mean values published from other research laboratories. DESIGN: Many samples of hair were collected carefully from a healthy man over a comparatively long period of time and were processed and analyzed under standard conditions. Extensive published data from other research laboratories also were reviewed and compared. RESULTS: Coefficients of variation for trace elements in hair of the donor ranged from 17 to 74% for the essential elements copper, selenium and zinc and from 53 to 121% for the potential intoxicants aluminum, cadmium and lead. The ratio of high mean to low mean for values published by others on hair samples from healthy people ranged from two for selenium and zinc to 18 for aluminum. CONCLUSIONS: Hair analysis should be based on a diagnostic hypothesis such as cadmium intoxication or copper deficiency rather than on the ease of analysis or attempts to explain vague symptoms because within-person variability is large and interlaboratory agreement on normal values is poor.

Dietary vitamin B12, sulfur amino acids, and odd-chain fatty acids affect the responses of rats to nickel deprivation.

An experiment was performed to ascertain whether changing the dietary intake of two substances, cystine and margaric acid (heptadecanoic acid), that affect the flux through pathways involving the two vitamin B12-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, would affect the interaction between nickel and vitamin B12. Rats were assigned to treatment groups of six in a fully crossed, four-factorial arrangement. The independent variables, or factors, were: per kg of fresh diet, nickel analyzed at 25 and 850 micrograms; vitamin B12 supplements of 0 and 50 micrograms; margaric acid supplements of 0 and 5 g; and L-cystine supplements of 0 and 12 g. The diet without cystine was marginally deficient in sulfur amino acids. Nickel affected growth, liver wt/body wt ratio (LB/BW), and a number of variables associated with iron, calcium, zinc, copper, and magnesium metabolism. Most of the effects of nickel were modified by the vitamin B12 status of the rat. In numerous cases, the interaction between nickel and vitamin B12 was dependent on, or altered by, the cystine or margaric acid content of the diet. Thus, the findings showed that the extent and the direction of changes in numerous variables in response to nickel deprivation varied greatly with changes in diet composition. These variables include those previously reported to be affected by nickel deprivation, including growth and the distribution or functioning of iron, calcium, zinc, copper, and magnesium. The findings also support the hypothesis that nickel has a biological function in a metabolic pathway in which vitamin B12 is important.

Studies of the interaction between boron and calcium, and its modification by magnesium and potassium, in rats. Effects on growth, blood variables, and bone mineral composition.

Two experiments were performed to confirm that boron interacts with calcium, and that this interaction can be modified by dietary magnesium and potassium in the rat. Upon manipulating the dietary variables listed above, it was found that under certain conditions, boron and calcium deprivation similarly affected several variables; for example, they both could be made to elevate plasma alkaline phosphatase activity and to depress femur calcium concentration. Under some dietary conditions, both boron and calcium deprivation affected some variables related to blood or iron metabolism. However, the effects of dietary boron and calcium on spleen weight/body weight ratio, hematocrit, and femur iron concentration generally were not similar. Femur copper, magnesium, phosphorus, and zinc also were affected by an interaction between boron and calcium under some dietary conditions. The findings show that there is a relationship between boron and calcium, but they do not clearly indicate the nature of the relationship. However, the data suggest that boron and calcium act on similar systems in the rat.

Concentration of boron and other elements in human foods and personal-care products.

The element boron is ubiquitous in the environment. Comparatively low concentrations of dietary boron affect several aspects of mineral metabolism in animals and human beings. Therefore, it is appropriate to determine precisely the concentration of boron in human foodstuffs and absorbed, inhaled, or ingested nonfood substances. In this article, we report the analyzed concentrations of boron and other elements in selected foods (animal products, water, condiments, confections, fruits, tuberized roots, vegetables, cereal grains, and spices) and personal-care products (analgesics, antibiotics, decongestants, antihistamines, dental hygiene products, gastric antacids, and laxatives). We conclude that daily intake of boron usually differs considerably between any two individuals for three main reasons. First, concentration of boron in water varies considerably according to geographic source. At some locations, boron in drinking water and water-based beverages may account for most of the total dietary boron intake. Second, individual food preference greatly influences daily intake of boron. Fruits, vegetables, tubers, and legumes have relatively much higher concentrations of boron than do cereal grains or animal tissues and fluids. Third, boron was determined to be a notable contaminant or major ingredient of many personal-care products.

Selected ultratrace elements in total parenteral nutrition solutions.

Ultratrace elements are potentially essential (eg. boron, molybdenum, nickel, and vanadium) or toxic (eg, aluminum and cadmium) in humans. Long-term total parenteral nutrition (TPN) patients can inadvertently receive significant amounts of ultratrace elements present as contaminants in TPN solutions. We determined the intake of selected ultratrace elements from a standard TPN solution and compared it with the amount reported to be absorbed from food in normal subjects. Contamination of TPN solutions with ultratrace elements was widespread and variable. The daily intakes of Mo, Ni, V. and Cd from this contamination were comparable to the amounts reported to be absorbed through the gastrointestinal tract in normal subjects. Al intake was high; B intake was low, approximately 10% of the amount absorbed by normal subjects. Thus, TPN solutions are contaminated with significant amounts of ultratrace elements. The biological significance of the intravenous infusion of these ultratrace elements is unclear and requires further investigation, particularly in home TPN patients.

Magnesium and methionine deprivation affect the response of rats to boron deprivation.

A series of nine experiments were done to obtain further evidence that boron might be involved in major mineral metabolism (Ca, P, and Mg), thus indicating that boron is an essential nutrient for animals. Eight factorially arranged experiments of 6-10 wk durations were done with weanling Sprague-Dawley male rats. One factorially arranged experiment was done with weanling spontaneously hypertensive rats. The variables in each experiment were dietary boron supplements of 0 and 3 micrograms g, and dietary magnesium supplements of either 200 (Experiments 1-3) or 100 (Experiments 4-9) and 400 micrograms/g. In Experiments 7 and 9, a third variable was dietary manganese supplements of 25 and 50 micrograms/g. Methionine status was varied throughout the series of experiments by supplementing the casein-based diet with methionine and arginine. Findings were obtained indicating that the severity of magnesium deprivation and the methionine status of the rat strongly influence the extent and nature of the interaction between magnesium and boron, and the response to boron deprivation. When magnesium deprivation was severe enough to cause typical signs of deficiency, a significant interaction between boron and magnesium was found. Generally, the interaction was characterized by the deprivation of one of the elements making the deficiency signs of the other more marked. The interaction was most evident when the diet was not supplemented with methionine and especially when the diet contained luxuriant arginine. Signs of boron deprivation were also more marked and consistent when the diet contained marginal methionine and luxuriant arginine. Among the signs of boron deprivation exhibited by rats fed marginal methionine were depressed growth and bone magnesium concentration, and elevated spleen wt/body wt and kidney wt/body wt ratios. Because the boron supplement of 3 micrograms/g did not make the dietary intake of this element unusual, it seems likely that the response of the rats to dietary boron in the present study were manifestations of physiological, not pharmacological, actions, and support the hypothesis that boron is an essential nutrient for the rat.

Dietary magnesium, manganese and boron affect the response of rats to high dietary aluminum.

Studies were done to ascertain whether dietary magnesium, manganese and boron affect the response of the rat to high dietary aluminum. Four factorially arranged experiments of 7 weeks duration were performed with weanling Sprague-Dawley male rats. The variables were the following supplements (microgram/g fresh diet): boron as boric acid, 0 and 3; aluminum as aluminum chloride, 0 and 1,000; and magnesium as magnesium acetate, 100 and 400 (experiments 1 and 4) or 100, 200 and 400 (experiments 2 and 3). In experiments 1 and 2, the diet was supplemented with 20 micrograms manganese/g as manganese acetate, in experiments 3 and 4 the supplement was 50 micrograms/g. High dietary aluminum seemed most toxic when dietary magnesium was low enough to cause a marked growth depression (100 micrograms/g). High dietary aluminum elevated the spleen weight/body weight and liver weight/body weight ratios in magnesium-deficient, but not in magnesium-adequate rats. High dietary aluminum depressed the concentrations of magnesium in bone more markedly in magnesium-deficient than adequate rats. On the other hand, aluminum seemed most toxic when dietary boron was not low. Aluminum more markedly depressed growth in boron-supplemented than boron-deprived rats. In the boron-deprived rats fed 400 micrograms magnesium/g of diet, high dietary aluminum (1,000 micrograms/g) apparently was beneficial, in experiments 2 and 3, hematocrit, and hemoglobin were actually normalized by high dietary aluminum. Plasma magnesium was significantly depressed by high dietary aluminum when the manganese supplement was 50 micrograms/g diet but not when it was 20 micrograms/g diet. On the other hand, growth was more markedly depressed by high dietary aluminum in boron-supplemented rats when the manganese supplement was 20 rather than 50 micrograms/g diet. The findings indicate that the response of rats to high dietary aluminum is influenced by magnesium, boron, and manganese nutriture.

Nickel influences iron metabolism through physiologic, pharmacologic and toxicologic mechanisms in the rat.

A study involving three experiments was done to ascertain whether the beneficial effect of nickel on hematopoiesis in moderately iron-deficient rats was due to physiologic and/or pharmacologic mechanisms. Female Sprague-Dawley rats were fed nickel supplements ranging from 0 to 100 micrograms/g in iron-low (15 micrograms Fe3+/g), iron-adequate (65 micrograms Fe3+/g), or iron-luxuriant (100 micrograms Fe3+/g) diets. The basal diet contained from 2 ng (experiment 3) to 36 ng (experiment 1) of nickel/g. At 10 weeks, both nickel deficiency and toxicity (100 micrograms/g diet) tended to depress hematopoiesis and markedly altered femur and liver trace element content in marginally iron-deficient rats. The alterations included elevated copper, iron and nickel, and depressed calcium and manganese in femurs. The pharmacologic action of nickel was indicated by the finding that high dietary nickel (5, 10, 20 or 50 micrograms/g) apparently stimulated hematopoiesis in marginally iron-deprived rats to a greater extent than dietary levels of nickel (0.1, 0.5 or 1.0 microgram/g) considered adequate for nutritional needs. High dietary nickel also elevated the iron content in liver of marginally iron-adequate rats. The findings indicate that nickel influences iron metabolism at physiologic, pharmacologic and toxic levels of intake. They also indicate that many previously reported signs of nickel deprivation, including effects on hematopoiesis, may have been misinterpreted and might be manifestations of pharmacologic actions of nickel.

Bioavailability of nickel in man: effects of foods and chemically-defined dietary constituents on the absorption of inorganic nickel.

By serial determination of the change in plasma nickel concentration following a standard dose of 22.4 mg of nickel sulfate hexahydrate containing 5 mg of elemental nickel, the bioavailability of nickel was estimated in human subjects. Plasma nickel concentration was stable in the fasting state and after an unlabeled test meal, but after the standard dose of nickel in water was elevated 48.8, 73.0, 80.0, and 53.3 microgram/1, respectively, at hours 1, 2, 3, and 4. Plasma nickel did not rise above fasting levels when 5 mg of nickel was added to two standard meals: a typical Guatemalan meal and a North American breakfast. When 5 mg of nickel was added to five beverages-whole cow milk, coffee, tea, orange juice, and Coca Cola-the rise in plasma nickel was significantly suppressed with all but Coca Cola. Response to nickel also was suppressed in the presence of 1 g of ascorbic acid. Phytic acid in a 2:1 molar ratio with nickel, however, did not affect the rise in plasma nickel. The chelate of iron and ethylenediaminetetraacetate, NaFeEDTA, an iron-fortifying agent suggested for application in Central America, slightly but not significantly depressed plasma nickel rise at 2 hours, whereas disodium EDTA depressed plasma nickel levels significantly below the fasting nickel curve at 3 and 4 hours postdose. These studies suggest that the differential responses of inorganic nickel to distinct foods, beverages, and chemically-defined dietary constituents could be important to human nutrition.

Interactions among nickel, copper, and iron in rats : Liver and plasma content of lipids and trace elements.

In two fully crossed, three-way, two by three by three, factorially arranged experiments, female weanling rats were fed a basal diet supplemented with iron at 15 and 45 µg/g, nickel at 0, 5, and 50 µg/g and copper at 0, 0.5, and 5 µg/g (Expt. 1) or 0, 0.25, and 12 µg/g (Expt. 2). Expt. 1 was terminated at 11 weeks, and Expt. 2 at 8 weeks because, at those times, some rats fed no supplemental copper and the high level of nickel began to lose weight, or die from heart rupture. The experiments showed that nickel interacted with copper and this interaction was influenced by dietary iron. If copper deficiency was neither very severe or mild, copper deficiency signs of elevated levels of total lipids and lipid phosphorus in liver and plasma, and cholesterol in plasma, were made more severe by supplemental dietary nickel. Rats in which nickel supplementation exacerbated copper deficiency did not exhibit a depressed level of copper in liver and plasma. Also, although iron deprivation enhanced the interaction between nickel and copper, iron deprivation did not significantly depress the level of copper in liver and plasma. The findings confirmed that, in rats, a complex relationship exists between nickel, copper, and iron, thus indicating that both the iron and copper status of experimental animals must be controlled before data about nickel nutriture and metabolism can be compared among studies.

Effect of form of iron on nickel deprivation in the rat : Liver content of copper, iron, manganese, and zinc.

In three fully crossed, factorially arranged, completely randomized experiments, female weanling rats were fed a basal diet (containing about 10 ng of nickel and 2.3 µg of iron/g) supplemented with graded levels of nickel and iron. Iron was supplemented to the diet in experiment 1 at levels of 0, 25, 50, and 100 µg/g as a mixture of 40% FeSO4·nH2O and 60% Fe2(SO4)3·nH2O; in experiment 2 at levels of 0, 12.5, 25, 50, and 100 µg/g as Fe2(SO4)3·nH2O; in experiment 3 at levels of 0, 25, and 50 µg/g as either the mixture of ferric-ferrous sulfates, or as ferric sulfate only. Nickel as NiCl2·3H2O was supplemented to the diet in experiment 1 at levels of 0, 5, and 50 µg/g; in experiment 2 at levels of 0 and 50 µg/g; and in experiment 3 at levels of 0 and 5 µg/g. Regardless of dietary nickel, rats fed no supplemental iron exhibited depressed iron content and elevated copper, manganese, and zinc contents in the liver. Nickel and iron did not interact to affect iron, manganese, and zinc in liver. Liver copper was inconsistently affected by an interaction between nickel and iron. Nickel deprivation apparently accentuated the elevation of the copper level in livers of severely iron-deficient rats. Experiment 3 showed that the form of dietary iron altered the effect of nickel deprivation on the iron content of the liver. When only ferric sulfate was supplemented to the diet, liver iron content was depressed in nickel-deprived rats. On the other hand, when the ferric-ferrous mixture was supplemented to the diet, nickel deprivation apparently elevated the iron content in the liver. The findings support the views that (1) parameters that are affected by an interaction between nickel and iron are limited in factorially arranged experiments, and (2) the form and level of dietary iron markedly influence the effect of nickel deprivation in the rat.

Interaction between nickel and iron in the rat.

The interaction between nickel and iron was confirmed in rat metabolism. In a fully-crossed, two-way, three by four, factorially designed experiment, female weanling rats were fed a basal diet supplemented with iron at 0, 25, 50, and 100 µg/g and with nickel at 0, 5, and 50 µg/g. The basal diet contained about 10 ng of nickel and 2.3 µg of iron/g. After nine weeks, dietary iron affected growth, hematocrit, hemoglobin, plasma cholesterol, and in liver affected total lipids, phospholipids, and the contents of copper, iron, manganese, and zinc. By manipulating the iron content of the diet, effects of dietary nickel were shown in rats that were not from dams fed a nickel-deprived diet. Nickel affected growth, hematocrit, hemoglobin, plasma alkaline phosphatase activity, plasma total lipids, and in liver affected total lipids, and the contents of copper, manganese, and nickel. The interaction between nickel and iron affected hematocrit, hemoglobin, plasma alkaline phosphatase activity, and plasma phospholipids, and in liver affected size, content of copper, and perhaps of manganese and nickel. In severely iron-deficient rats, the high level of dietary nickel partially alleviated the drastic depression of hematocrit and hemoglobin, and the elevation of copper in liver. Simultaneously, high dietary nickel did not increase the iron level in liver and was detrimental to growth and appearance of severely iron-deficient rats. In nickel-deprived rats fed the borderline iron-deficient diet (25 µg/g) hematocrit and hemoglobin also were depressed. However, 5 µg Ni/g of diet were just as effective as 50 µg Ni/g of diet in preventing those signs of nickel deprivation. The findings in the present study suggested that nickel and iron interact with each other at more than one locus.

Effect of dietary nickel and iron on the trace element content of rat liver.

The level and/or form of dietary iron, dietary nickel, and the interaction between them affected the trace element content of rat liver. Livers were from the offspring of dams fed diets containing 10-16 ng, or 20 µg, of nickel/g. Dietary iron was supplied as ferric chloride (30 µg/g) or ferric sulfate (30 µg, or 60 µg). In nickel-deprived rats fed 60 µg of iron/g of diet as ferric sulfate, at age 35 days, levels of iron and zinc were depressed in liver and the level of copper was elevated. At age 55 days, iron was still depressed, copper was still elevated, but zinc also was elevated. In rats fed 30 µg of iron/g of diet as ferric chloride, liver iron content was higher in nickel-deprived than in nickel-supplemented rats at 30, but not at 50, days of age. Also manganese and zinc were lower in nickel-deprived than in nickel-supplemented rats at age 35 days if their dams had been on experiment for an extended period of time (i.e., since age 21 days). Thus, the levels of copper, iron, manganese, and zinc in liver were affected by nickel deprivation, but the direction and extent of the affects depended upon the iron status of the rat.

Intake of nickel and vanadium by humans. A survey of selected diets.

The nickel and vanadium contents of nine institutional diets were determined by atomic absorption spectrometry with background correction. The following values were obtained for nickel: mean concentration, 0.27 +/- 0.02 microgram/g (dry weight); range, 0.19 and 0.41 microgram/g; mean intake, 165 +/- 11 microgram/day or 75 +/- 10 microgram/1000 cal. The respective values for vanadium were: 0.032 +/- 0.004 microgram/g (dry weight); 0.019 to 0.050 microgram/g; 20.4 +/- 2.3 microgram/day or 8.9 +/- 1.0 microgram/1000 cal. Thus, vanadium is present at approximately one order of magnitude less than nickel.