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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 199 records · Page 11Linked to original sources

Oral iron, dietary ligands and zinc absorption.

The effect of iron on zinc absorption in humans was investigated by using 65Zn and whole-body counting after 2 wk. Increasing the molar ratio of ferrous iron (with ascorbic acid) to zinc from 1:1 to 2.5:1 did not affect absorption of zinc from water when given in a fasting state; 59 and 58% was absorbed, respectively. However, at an Fe:Zn ratio of 25:1, zinc absorption from water decreased significantly to 34%. When oral iron in the same ratio to zinc was given with a meal, no inhibitory effect was observed (25, 23 and 22%, respectively). Addition of the zinc ligand, histidine, to the water solution decreased the inhibitory effect of the higher dose of iron, resulting in a zinc absorption of 47%. Two weeks of iron preloading did not affect zinc absorption from water. The results demonstrate that when a multimineral supplement is taken on an empty stomach, excessive iron levels can negatively affect zinc absorption. Intake of the supplement with a meal or with a zinc ligand (such as histidine) may overcome this inhibitory effect.

Administration, Oral↗

Manganese deficiency: effects on susceptibility to ethanol toxicity in rats.

Previous studies have shown that manganese (Mn) deficiency in rats results in reduced activity of manganese superoxide dismutase (MnSOD) and increased levels of mitochondrial lipid peroxidation. These findings suggested to us that the Mn-deficient rat may be especially susceptible to the toxic effects of ethanol, as the metabolism of this compound results in production of superoxide anion. Offspring from Mn-sufficient and Mn-deficient adult rats were given either 20% (wt/vol) ethanol or distilled-deionized water as their drinking fluid for 14 d. Response to ethanol feeding was different between Mn-sufficient and deficient rats as evidenced by severe reductions in caloric intake and body weight observed in the Mn-deficient rats. Furthermore, after 14 d of ethanol feeding, these rats were extremely lethargic and in poor physical condition. Although Mn-sufficient rats responded similarly to the deficient rats during the first 6 d of ethanol feeding, they increased their caloric intake and body weight during the remainder of the experimental period. MnSOD activity in the ethanol-fed Mn-sufficient and Mn-deficient rats was similar, thus the alcohol-induced toxicity observed in the deficient rats was not due to reduced MnSOD activity. Iron-induced lipid peroxidation may be one of the mechanisms leading to the toxicity observed, as ethanol feeding resulted in liver Fe levels that were 30% higher than those in Mn-deficient rats that were not fed ethanol.

Animals↗

Effects of varying dietary iron on the expression of copper deficiency in the growing rat: anemia, ferroxidase I and II, tissue trace elements, ascorbic acid, and xanthine dehydrogenase.

The effect of dietary iron on the development of copper-deficiency anemia in the growing rat was investigated. For up to 80 d, female rats (75 g) were fed purified diets containing adequate, marginal or low levels of iron, and either 0.7 or 10 ppm copper. Hemoglobin levels and factors postulated to affect liver iron mobilization, including ferroxidase (Fox) I and II, ascorbate and liver xanthine dehydrogenase (XDH) were assayed. By d 7, Fox I activity in the copper-deficient groups was 10% that of the copper-sufficient groups; thereafter, Fox I activity remained low, and was not affected by dietary iron. Fox II activity in the copper-deficient groups after d 28 was 50-75% of values from rats adequate in copper. On d 49, hemoglobin levels in the copper-deficient groups were lower than in the copper-sufficient groups fed low and marginal levels of iron, but were similar to those fed adequate iron. Liver iron was similar in both groups fed adequate iron, but was higher in the copper-deficient than in the copper-sufficient rats fed low or marginal levels of iron. Copper deficiency tended to result in slightly lower ascorbate levels on d 80 at all levels of iron. Liver XDH activity tended to be lower in the copper-deficient groups than in the copper-sufficient groups on d 28 and 49. These results show that copper deficiency may impair liver iron mobilization in the growing rat if dietary iron is low. Possible mechanisms include decreased Fox activity and/or decreased iron reduction by ascorbate or XDH.

Anemia↗

Determinants of copper-deficiency anemia in rats.

Indicators of copper and iron metabolism were studied in pregnant rats and their 90-d-old offspring fed copper-sufficient or copper-deficient diets containing marginal or adequate levels of iron from the beginning of pregnancy until the offspring were 90 d of age. Offspring had more severe signs of copper deficiency (including anemia, hypertrophy of the heart, decreased activity of ferroxidase I and II, depression of growth and death) than the dams. In both dams and offspring, copper deficiency resulted in anemia when dietary iron was marginal but not when it was adequate. Liver iron was elevated in copper-deficient male offspring, but not in female offspring. Anemia and growth retardation were more pronounced in copper-deficient males than in females, despite similarly low levels of ferroxidase I and II. Iron absorption was reduced by copper deficiency only in female offspring. Activity of 59Fe in various tissues 6 or 48 h after gavage did not reveal any other effect of copper deficiency on iron metabolism. Thus age at the time copper-deficient diets were introduced, sex and dietary iron strongly influence the effect of copper deficiency.

Aging↗

Inorganic constituents of breast milk from vegetarian and nonvegetarian women: relationships with each other and with organic constituents.

Changes in concentrations of minerals, trace elements, protein, lactose and total lipids during 20 mo of lactation and correlations between levels of these milk constituents were studied in a carefully defined set of 222 milk samples collected from 52 women, one-half of whom were vegetarians. Milk samples from vegetarians and those from nonvegetarians contained similar levels of iron, copper, zinc, sodium, potassium, calcium, magnesium, lactose and fat. Following a brief but sharp initial decrease, levels of protein and iron did not change significantly between mo 2 and 20 of lactation. Levels of zinc, copper, sodium and potassium declined for the first 6 mo of lactation. Levels of lipid, sodium and zinc increased during later months of lactation while that of calcium decreased. Levels of lactose, copper, potassium and magnesium remained unchanged during mo 7-20. Stepwise multiple regression analysis showed positive correlations between levels of three pairs of inorganic constituents during the first 6 mo of lactation: copper and zinc, copper and potassium, and potassium and calcium. During the subsequent 14 mo of lactation, potassium was correlated with copper. The level of iron was positively correlated with that of lipid, while that of calcium was negatively correlated with that of lipid. These relationships, and others reported in the paper, are discussed in relation to current hypotheses of the mechanism of milk secretion and the binding of inorganic to organic milk constituents.

Adult↗

Calcium binding by alpha-lactalbumin in human milk and bovine milk.

The metal-binding property of alpha-lactalbumin (alpha-LA) in human milk was studied and compared to that of bovine milk alpha-LA. Gel filtration on Sephadex G-75 at physiological pH and ionic strength separated alpha-LA in human and bovine milk from most other proteins. The only metal ion associated with alpha-LA under these conditions was Ca2+. Minor protein contaminants were removed by ion-exchange chromatography, and the ratio of Ca2+:alpha-LA was determined in the isolated protein preparations. Concentrations of alpha-LA in mature human milk were between 1.03 and 1.57 mg/ml; the Ca2+ concentration bound to alpha-LA varied, yielding a molar ratio of Ca2+:alpha-LA of approximately 1:1 (0.82-1.41 mol Ca2+/mol alpha-LA) in mature milk. Gel filtration with excess Ca2+ in the running buffer showed that there is another weaker binding site for Ca2+, but this binding does not occur under physiological conditions. Less Ca2+ was bound to bovine alpha-LA (0.6-0.9 mol Ca2+/mol alpha-LA) than to human alpha-LA. Calcium binding was abolished at pH 3.0 and resulted in a substantial increase in the hydrodynamic radius of alpha-LA. Reconstitution of human alpha-LA with Ca2+ and other divalent cations at native pH (6.8) and ionic strength showed a binding specific for Ca2+. Since only 1% of calcium from human milk and 0.15% from bovine milk is alpha-LA bound, alpha-LA is probably unimportant with respect to calcium nutrition of the infant. However, the metal binding of alpha-LA may have a biological significance through its role in the lactose synthase complex.

Animals↗

Food choices of vegetarians and nonvegetarians during pregnancy and lactation.

Data on food choices and nutrient intake were obtained from 60 lactating women, including 29 vegetarians. The most common changes in consumption patterns during pregnancy were increased intake of high-protein foods, especially milk products, and decreased intake of coffee, tea, and alcohol. The changes were partially based on food cravings and/or aversions. In addition to high-protein foods, some of the women craved fruits and sweets. Items most commonly eliciting aversive reactions were vegetables, strong-smelling and strong-tasting combination dishes, and greasy foods. Aversions to coffee, tea, and alcohol were almost as frequent as those to greasy foods. Nutrient intake during lactation was measured using 24-hour recalls and 2-day diet records that also considered dietary supplements. A total of 332 intake records were evaluated relative to the RDAs for lactating women. Mean energy intake was 2,200 kcal (88% of the recommendation), and mean protein intake was 86 gm (134% of the RDA). Mean nutrient intakes from diet alone ranged from 89% of the RDA for iron to 154% for vitamin A; mean intakes from diet plus supplements ranged from 133% of the RDA for calcium to 581% of the RDA for thiamin. Dietary supplementation provided a substantial part of the intake of some nutrients; for most women, however, the RDAs were met by diet alone.

Adult↗

Breast-feeding among teenage mothers: milk composition, infant growth, and maternal dietary intake.

Information on breast-feeding was obtained from 25 mothers recruited from four high school programs for teenaged parents. Subjects were visited monthly 1-9 times (mean 3.7 visits) during the first 10 months of lactation to measure infant growth and maternal dietary intake and to collect a breast milk sample. Of 24 mothers visited more than once, 21 (88%) breast-fed for more than 3 months, and at least nine continued beyond 6 months. Compared to the nutrient content of milk samples from adult women, milk of teenage mothers was significantly lower in lactose, magnesium, calcium, potassium, and sodium. However, the differences in magnesium, calcium, and potassium may have been due to differences in the timing of sample collection. On the basis of infant growth, milk volume was judged to be adequate for 88% of the infants. Mean maternal energy and protein intakes were 2,897 kcal and 115 g, respectively; mean intakes of calcium, potassium, vitamin A, riboflavin, niacin, and vitamin C exceeded the National Research Council's Recommended Dietary Allowances (RDA) for lactation, while iron and thiamine intakes averaged 84% and 94% of the RDA, respectively. It is concluded that with active counseling teenage mothers are capable of successful lactation.

Adolescent↗

Molecular localization of copper and zinc in rat fetal liver in dietary and drug-induced copper deficiency.

The teratogenicity of copper deficiency is well known, but underlying mechanisms have not been delineated. One method of studying the biochemical lesions of copper deficiency is the use of chelating drugs with different chemical characteristics. The teratogenicity of a copper deficient diet and of diets containing either D-penicillamine or triethylenetetramine is quite different, although all three diets result in decreased fetal liver copper levels. Feeding D-penicillamine can result in decreased fetal liver zinc, while feeding triethylenetetramine can result in increased fetal liver zinc. The effect of these three diets on fetal liver copper and zinc molecular localization was determined. Gel filtration showed that fetal liver copper and zinc in controls was localized in 3 fractions with MWs of greater than 50,000 (H), 30,000 (I) and 8-10,000 (L). Independent of dietary treatment, as liver copper diminished, copper was missing first from the L peak, then the I peak and with severe deficiency, from the H peak. Drug induced increases and decreases in fetal liver zinc were reflected in the L peak. These data suggest that the absolute levels of copper in the liver of the term fetus determines the distribution of the element among its binding ligands.

Abnormalities, Drug-Induced↗

Iron, copper, zinc, calcium, and magnesium in human milk fat.

The trace elements iron, copper, and zinc and the minerals calcium and magnesium have been found associated to human milk fat. After solubilization of milk fat globule membranes with detergent, the major part of these elements within the fat fraction were found in the more hydrophilic outer fat globule membrane: Fe 61%, Cu 73%, Zn 64%, Ca 67%, and Mg 71%. Most of the remainder was found in the more hydrophobic inner membrane, while only small amounts of the elements were associated with the core triglyceride fraction. Gel filtration chromatography on Sepharose CL-6B indicates the major iron- and zinc-binding proteins in the outer membrane are xanthine oxidase and alkaline phosphatase.

Calcium↗

The effect of individual components of soy formula and cows' milk formula on zinc bioavailability.

Zinc absorption from human milk, cows' milk formulas, and soy formulas was studied in human adults by a radioisotope technique using 65Zn and whole body counting. Individual dietary components were investigated for effects on zinc absorption. Phytate was found to have a strong inhibitory effect on zinc absorption; addition of phytate to cows' milk formula (yielding a phytate concentration similar to that of soy formula) resulted in a decrease in zinc absorption from 31 to 16% similar to the absorption for soy formula (14%). Carbohydrate source, calcium, and zinc levels of the diet did not affect zinc absorption significantly. Iron supplementation of cows' milk formula decreased zinc absorption from 24 to 18% although this decrease was not found to be significant (p less than 0.1). Absorption of zinc from a whey-adjusted cows' milk formula was higher (31%) than from a nonmodified cows' milk formula (22%). Increasing the zinc supplementation level in cows' milk formula but not in soy formula increased zinc absorption to approximate that from breast milk. It is suggested that reduction of phytate content of soy formula may be a more effective avenue of modification than increased level of zinc supplementation.

Absorption↗

Zinc-copper interactions in the pregnant rat: fetal outcome and maternal and fetal zinc, copper and iron.

The interaction between zinc and copper in the pregnant rat was investigated by feeding Sprague-Dawley rats, from mating to term, diets that varied in zinc and copper concentrations. A factorial design was used with diets containing 1, 10, 100 or 1000 micrograms zinc/gram and 0.5, 5, 10 or 100 micrograms copper/gram. Malformations were found only in fetuses from rats fed the zinc-deficient diets (1 microgram/g), and the frequency of malformed fetuses increased as concentration of dietary copper increased. Maternal and fetal tissues of rats fed diets deficient in either zinc or copper were significantly lower in these elements than were those of rats fed a control diet. An antagonistic effect of dietary zinc on maternal and fetal tissue copper concentration was observed. The concentration of fetal liver zinc from rats fed a copper-deficient diet was significantly higher than controls. The concentration of iron in maternal and fetal tissues was significantly affected by the level of dietary zinc, with values highest in the zinc-deficient groups. Maternal plasma cholesterol and triglyceride levels were significantly lower than normal in the zinc-deficient animals. These data show that when the concentration of zinc in the diet is deficient an interaction can occur between dietary zinc and copper such that high levels of copper potentiate the teratogenicity of zinc deficiency.

Animals↗

Retention and distribution of iron added to cow's milk and human milk as various salts and chelates.

Iron supplementation of infant formulas is recommended by most national and international organizations, but the optimal form of supplementation has not been determined. We have compared the bioavailability and tissue distribution of iron from four iron chelates and two commonly used iron salts. Weanling C57BL/6J mice were fed for 1 week an evaporated cow's milk diet supplemented with vitamins and minerals (except for iron). Following the adjustment period, mice were divided into 12 groups of 20 each. Six groups continued to receive the cow's milk diet for 18 hours, while the other six groups were fed a similar diet based on human milk. Individual groups received a single dose of milk radioactively labeled with Fe(II)Cl2, Fe(II)SO4, Fe(III)NTA, Fe(III)EDTA, Fe(III)citrate or Fe(III)lactobionate. Wholebody retention was measured after 4 days; animals were then killed and individual tissues were counted for radioactivity. Iron from FeCl2, FeSO4 and FeNTA were the best retained from both milk diets. Fe citrate had a significantly lower iron retention than all other groups in either diet and is probably not an effective chelate for delivering iron to milk diets. Iron bioavailability was higher from the human milk diets than from the cow's milk diets from all vehicles used except citrate and lactobionate. Absorption of Fe citrate was similar from the two milk diets, while percent retention from Fe lactobionate was higher from cow's milk than from human milk. Tissue distribution of retained iron was similar for the milk diets and among the groups, indicating that, once absorbed, iron from the different vehicles is metabolized in a similar manner.

Animals↗

Supplementation of milk with iron bound to lactoferrin using weanling mice. II: Effects on tissue manganese, zinc, and copper.

Iron supplementation is recommended for formula-fed infants, and it is currently suggested that iron be supplemented in formulas at a minimum of 6 mg/L. A negative side effect of iron supplementation, however, may be a reduction in the absorption of elements with similar physicochemical properties. We investigated this possibility by evaluating the impact of iron supplementation at 6 mg/L on tissue concentrations of zinc, copper, and manganese. Weanling mice fed a supplemented diet for 4 weeks had markedly lower tissue manganese concentrations than mice fed a nonsupplemented diet. Tissue zinc and copper levels were only marginally affected. The potential negative effect of iron supplementation on manganese status in the human infant should be evaluated.

Animals↗

Breast milk volume and composition during late lactation (7-20 months).

Breast milk composition of 119 samples collected by 46 women during months 7-20 of lactation was compared with composition of 101 samples collected at 4-6 months. Breast milk intake of 10 infants was determined by test-weighing for 1 or more months during months 7-16 of lactation. Longitudinal decreases in milk concentrations of zinc, copper, and potassium, previously documented for the first 6 months, continued into the second 6 months, while protein, iron, and sodium concentrations showed no further decline. Lactose, fat, calcium, and magnesium concentrations were similar to those in earlier stages of lactation. Weaning was associated with significant changes in milk composition: When milk volume fell below 300 ml/day, there was an increase in protein and sodium and a decrease in lactose, calcium, and zinc. Breast milk intake of infants not supplemented with cow's milk or formula averaged 875 ml/day (93% of total energy intake) at 7 months and 550 ml/day (50% of total energy intake) at 11-16 months. Total energy intake increased from 610 to 735 kcal/day, but energy intake per kilogram remained constant at a relatively low 70-79 kcal/kg/day. Our results suggest the need for further studies of nutrient intake and requirements of breast-fed infants during late lactation.

Adult↗