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2.
Int J Vitam Nutr Res ; 84 Suppl 1: 40-51, 2014.
Article in English | MEDLINE | ID: mdl-25537105

ABSTRACT

Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the “gold standard” for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a population’s dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.


Subject(s)
Indicator Dilution Techniques , Isotope Labeling , Vitamin A/metabolism , Humans , Liver/metabolism , Nutritional Status , Vitamin A Deficiency/epidemiology
3.
Int J Vitam Nutr Res ; 84 Suppl 1: 52-9, 2014.
Article in English | MEDLINE | ID: mdl-25537106

ABSTRACT

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of ß-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.


Subject(s)
Indicator Dilution Techniques , Isotope Labeling , Vitamin A/metabolism , Humans , Vitamin A Deficiency/diagnosis
4.
J Nutr ; 141(3): 391-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21248199

ABSTRACT

Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.


Subject(s)
Bone Resorption/prevention & control , Calcium/metabolism , Calcium/urine , Dietary Proteins/therapeutic use , Meat , Osteogenesis , Osteoporosis, Postmenopausal/prevention & control , Aged , Biomarkers/blood , Biomarkers/urine , Bone and Bones/metabolism , Calcium/blood , Calcium Radioisotopes , Cross-Over Studies , Dietary Proteins/adverse effects , Female , Humans , Insulin-Like Growth Factor I/analysis , Intestinal Absorption , Meat/adverse effects , Middle Aged , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/urine , Parathyroid Hormone/blood , Whole-Body Counting
5.
Int J Vitam Nutr Res ; 80(4-5): 257-62, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21462108

ABSTRACT

Several bioavailability algorithms have been proposed for iron and zinc, confirming the need for these tools while emphasizing the challenge of deriving algorithms with accepted accuracy. This manuscript briefly reviews current evidence on the accuracy of proposed algorithms. Iron absorption is strongly influenced by both body iron status and dietary availability, and most evidence suggests that these do not interact. There is considerable evidence of a logarithmic relationship between percent iron absorption and serum ferritin that allows a simple and accurate computation of how human iron status affects absorption (in the absence of inflammation). Computing the effect of dietary variation on nonheme iron absorption has been challenging because of multiple influential dietary factors and incomplete knowledge of their chemical characteristics, food composition, interactions, and dose-response relationships. At present there is no fully validated algorithm for dietary iron bioavailability. Predicting zinc absorption is less complex. Fractional zinc absorption is substantially influenced by the amount of zinc consumed, and this factor, together with ingested phytic acid, account for a considerable degree of the variance. A multivariate saturation model based on these two variables has been derived using data from multiple studies and independently validated with a single large data set.


Subject(s)
Algorithms , Intestinal Absorption , Iron, Dietary/blood , Nutritional Status , Zinc/blood , Biological Availability , Biomarkers/blood , Ferritins/blood , Humans , Phytic Acid/blood
6.
J Nutr Biochem ; 21(4): 297-303, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19369052

ABSTRACT

The nutritional influence of zinc on markers of bone extracellular matrix resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15 or 30 microg Zn/g diet for 24 days. Femur zinc increased substantially as zinc increased from 5 to 15 microg/g diet and modestly between 15 and 30 microg/g (P<.05). By morphological assessment, trabecular bone increased steadily as dietary zinc increased to 30 microg/g. Increasing dietary zinc tended to decrease Zip2 expression nonsignificantly and elevated the relative expression of metallothionen-I at 15 but not 30 microg Zn/g diet. Femur osteoclastic resorption potential, indicated by matrix metalloproteinases (MMP-2 and MMP-9) and carbonic anhydrase-2 activities decreased with increasing dietary zinc. In contrast to indicators of extracellular matrix resorption, femur tartrate-resistant acid and alkaline phosphatase activities increased fourfold as dietary zinc increased from 2.5 to 30 microg Zn/g. Likewise, 15 or 30 microg Zn/g diet resulted in maximum relative expression of osteocalcin, without influencing expression of core-binding factor alpha-1, collagen Type 1 alpha-1, or nuclear factor of activated T cells c1. In conclusion, increased trabecular bone with additional zinc suggests that previous requirement estimates of 15 microg Zn/g diet may not meet nutritional needs for optimal bone development. Overall, the up-regulation of extracellular matrix modeling indexes and concomitant decrease in resorption activities as dietary zinc increased from 2.5 to 30 microg/g provide evidence of one or more physiological roles for zinc in modulating the balance between bone formation and resorption.


Subject(s)
Bone Development/physiology , Bone Matrix/physiology , Bone Resorption/prevention & control , Calcification, Physiologic/physiology , Osteoclasts/cytology , Osteoclasts/physiology , Zinc/administration & dosage , Animals , Biomarkers , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Cell Differentiation , Collagen Type I, alpha 1 Chain , Diet , Femur/chemistry , Femur/growth & development , Femur/metabolism , Gene Expression Regulation , Growth Plate/anatomy & histology , Growth Plate/enzymology , Growth Plate/growth & development , Male , Metallothionein/genetics , Metallothionein/metabolism , Osteocalcin/genetics , Osteocalcin/metabolism , RNA, Messenger/metabolism , Random Allocation , Rats , Tibia/anatomy & histology , Tibia/growth & development , Zinc/analysis , Zinc/physiology
7.
J Am Coll Nutr ; 28(2): 177-83, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19828903

ABSTRACT

OBJECTIVE: To determine if human Zn absorption adapts to chronic high Zn intakes. METHODS: Zn absorption was measured at 0, 8, and 16 wk in healthy postmenopausal women who consumed controlled diets with approximately 5 mg Zn from food, supplemented to 14 (n = 6), 32 (n = 3), or 47 (n = 3) mg Zn/d for 22 wk. Zn absorption for 1 day was determined by (65)Zn-labeling of meals and whole body scintillation counting. RESULTS: At wk 0, less Zn was absorbed from diets with 14, compared with 32 or 47 mg/d (4.6, 8.7, and 10.3 mg/d, respectively; pooled SE = 0.9; p < 0.05). These differences were not apparent at wk 8 (5.4, 5.8, 6.4; NS) and became negligible by wk 16 (5.0, 5.0, 5.1; NS). Plasma Zn concentrations were unaffected. The results are consistent with a saturation response model of Zn absorption. CONCLUSION: Within several weeks, postmenopausal women biologically adapted to absorb a relatively uniform amount of 5 mg Zn/d when controlled, Zn-supplemented diets supplied consistent Zn intakes between 14 and 47 mg/d.


Subject(s)
Adaptation, Physiological , Dietary Supplements , Postmenopause/metabolism , Zinc/pharmacokinetics , Aged , Diet , Female , Humans , Intestinal Absorption , Middle Aged , Zinc/administration & dosage
8.
Am J Clin Nutr ; 89(6): 1792-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19386738

ABSTRACT

BACKGROUND: Iron excretion measured by isotope dilution has been a primary basis for the factorial derivation of recommendations for iron intake, but the results have been available for men only. OBJECTIVE: The objective of this study was to confirm iron excretion measurements in healthy men and extend them to women. DESIGN: The turnover rate of 55Fe that had been administered > or =1 y earlier was determined from blood sampled semiannually for up to 3 y from 53 subjects in the community. Body iron was determined from hemoglobin, serum ferritin, and transferrin receptor. Complete menstrual collections were obtained from 13 women. RESULTS: The total median (range) iron excretion was 1.18 (0.11-2.07) mg/d for 29 men, 1.58 (0.65-4.88) mg/d for 19 menstruating women, and 0.99 (0.86-1.57) for 5 postmenopausal women. When hormonal contraceptive users were omitted, the median for 15 menstruating women increased to 1.66 mg/d. The distribution of iron excretion was normal for the men and postmenopausal women and was highly skewed for the menstruating women; menstrual iron accounted for 90% of the variation. Iron excretion was not strongly related to body weight. Body iron in menstruating women decreased somewhat (by 4.6%) in the men and tended to increase (by 1.5%) during the study. CONCLUSIONS: The results extend direct iron excretion measurements in men to include similar measurements in women. The results emphasize the wide range of iron excretion in humans, which results in a 40-fold range of requirements for absorbed iron. This trial was registered at clinicaltrials.gov as NCT00755105.


Subject(s)
Iron/metabolism , Adult , Body Weight , Female , Ferritins/blood , Half-Life , Hemoglobins/analysis , Humans , Iron/blood , Male , Menstruation/metabolism , Middle Aged , Sex Factors
9.
Am J Clin Nutr ; 89(5): 1357-65, 2009 May.
Article in English | MEDLINE | ID: mdl-19279077

ABSTRACT

BACKGROUND: The effect of meat protein on calcium retention at different calcium intakes is unresolved. OBJECTIVE: The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium. DESIGN: In a randomized controlled feeding study with a 2 x 2 factorial crossover design, healthy postmenopausal women (n = 27) consumed either approximately 675 or approximately 1510 mg Ca/d, with both low and high protein (providing 10% and 20% energy) for 7 wk each, separated by a 3-wk washout period. After 3 wk, the entire diet was extrinsically labeled with (47)Ca, and isotope retention was monitored by whole-body scintillation counting. Clinical markers of calcium and bone metabolism were measured. RESULTS: High compared with low dietary protein significantly increased calcium retention from the low-calcium (29.5% compared with 26.0% absorbed) but not the high-calcium diet (18% absorbed). For the low-calcium diet, this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion. Protein-related calciuretic effects were independent of dietary calcium. Testing at 1, 2, 3, 5, and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion. High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase, or tartrate-resistant acid phosphatase. CONCLUSIONS: In healthy postmenopausal women, a moderate increase in dietary protein, from 10% to 20% of energy, slightly improved calcium absorption from a low-calcium diet, nearly compensating for a slight increase in urinary calcium excretion. Under practical dietary conditions, increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health.


Subject(s)
Calcium, Dietary/pharmacology , Calcium/blood , Dietary Proteins/pharmacology , Aged , Aged, 80 and over , Ammonia/urine , Body Mass Index , Calcium/urine , Calcium Radioisotopes , Cross-Over Studies , Diet, Protein-Restricted , Energy Intake , Female , Humans , Middle Aged , Postmenopause
10.
Am J Clin Nutr ; 89(3): 839-43, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19176739

ABSTRACT

BACKGROUND: Although calcium inhibits zinc bioavailability in rats, especially from high-phytate diets, the effect of calcium on zinc absorption by humans from practical diets remains unclear. OBJECTIVE: The objective was to test the inhibitory effect of dietary calcium, in Western diets with high and low phytate content, on zinc absorption. DESIGN: Using a 2 x 2 factorial design, zinc absorption was determined in 10 healthy women from 1-d diets with moderate and high calcium contents of approximately 700 and 1800 mg/d and low and high phytate contents of approximately 440 and 1800 mg/d. Absorption was measured by using extrinsically added (65)Zn and subsequent whole-body scintillation counting. RESULTS: Mean (+/-SE) fractional zinc absorption was 32.8 +/- 2.3% from the moderate-calcium, low-phytate diet; 26.9 +/- 2.4% from the moderate-calcium, high-phytate diet; 39.4 +/- 2.4% from the high-calcium, low-phytate diet; and 26.2 +/- 2.3% from the high-calcium, high-phytate diet. The respective values for absolute zinc absorption were 3.8 +/- 0.3, 3.0 +/- 0.3, 4.5 +/- 0.3, and 3.2 +/- 0.3 mg/d. Phytate significantly reduced fractional zinc absorption by approximately 10 percentage points and reduced absolute zinc absorption by 25%, or approximately 1 mg/d. Differences in dietary calcium did not affect zinc absorption, regardless of a high or low dietary phytate content. CONCLUSIONS: In healthy women consuming 1-d menus of ordinary foods (some fortified with calcium), dietary phytate reduces zinc absorption, but calcium does not impair zinc absorption, regardless of whether dietary phytate is low or high.


Subject(s)
Calcium, Dietary/administration & dosage , Phytic Acid/administration & dosage , Zinc/pharmacokinetics , Adult , Female , Humans , Intestinal Absorption , Middle Aged , Scintillation Counting , Young Adult , Zinc/administration & dosage , Zinc Radioisotopes
11.
J Nutr ; 138(8): 1462-8, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18641192

ABSTRACT

Although calcium (Ca) supplementation increases bone density, the increase is small and the effect on bone strength and fracture risk is uncertain. To investigate if bone mass, morphology, and biomechanical properties are affected by deficient to copious dietary Ca concentrations, the long bones (tibia and femur) of growing female Sprague-Dawley rats (8/group) were assessed after 13 wk of consuming 1, 2, 3, 4, 5, 6, or 7 g Ca/kg of a modified AIN-93G diet. Dietary phosphorous (P) and vitamin D remained constant at recommended concentrations. The assessment included mineralization, density, biomechanical properties of breaking by a 3-point flexure test, and morphological properties by microcomputed topography scanning of trabecular bone of the proximal tibia metaphysis. Dietary treatment did not affect food intake, weight gain, renal and muscle Ca concentrations, and bone hydroxyproline. All bone parameters measured were significantly impaired by Ca deficiency in rats fed the diet containing 1 g Ca/kg. Modest impairments occurred with some parameters (bone density, biomechanical bending moment, modulus of elasticity, and stress) in rats fed 2 g Ca/kg, but all parameters stabilized between 2 and 3 g/kg diet, with no differences between 3 and 7 g/kg. The results suggest that a threshold response in bone Ca retention or bone mass at approximately 2.5 g Ca/kg diet is associated with similar threshold responses in bone breaking strength and related biomechanics as well as trabecular structural properties. There was no evidence of a relative P deficiency or of improved or impaired bone strength and structure as Ca intakes increased beyond those needed to maximize bone density.


Subject(s)
Bone Density/drug effects , Bone and Bones/drug effects , Bone and Bones/physiology , Calcium/metabolism , Calcium/pharmacology , Alkaline Phosphatase/blood , Animals , Biomechanical Phenomena , Bone and Bones/anatomy & histology , Bone and Bones/chemistry , Calcium/administration & dosage , Dose-Response Relationship, Drug , Female , Femur/anatomy & histology , Hydroxyproline/metabolism , Kidney/chemistry , Kidney/metabolism , Muscle, Skeletal/chemistry , Muscle, Skeletal/metabolism , Phosphorus/analysis , Rats , Rats, Sprague-Dawley , Tibia/anatomy & histology
12.
Am J Clin Nutr ; 87(5): 1336-45, 2008 May.
Article in English | MEDLINE | ID: mdl-18469257

ABSTRACT

BACKGROUND: An understanding of the relations among dietary zinc intake, bioavailability, and absorption is necessary for making dietary intake recommendations. OBJECTIVES: We aimed to assess adaptation in human zinc absorption to controlled differences in zinc and phytate intakes and to apply the results to predictive models. DESIGN: In 3 experiments, radiotracers were used to assess zinc absorption by healthy adults (n = 109) from controlled diets, before and after 4 or 8 wk of dietary equilibration. Subjects consumed 4-29 mg Zn/d from 1 of 10 diets, 5 with molar ratios of phytate to zinc from 2 to 7 and 5 with ratios from 15 to 23. RESULTS: Absorptive efficiency was inversely related to dietary zinc from both low- and high-phytate diets. In response to low zinc intakes (<11 mg/d) for 4-8 wk, zinc absorption was up-regulated to as high as 92%, but only if the diets were low in phytate. The results help validate and refine a published saturable transport model that predicts zinc absorption from dietary zinc and phytate. Possible biomarkers of impaired zinc status, including erythrocyte osmotic fragility, in vitro erythrocyte (65)Zn uptake, and leukocyte expression of the zinc transport proteins Zip1 and ZnT1, were unresponsive to dietary zinc content. CONCLUSIONS: Humans absorbed zinc more efficiently from low-zinc diets and adapted to further increase zinc absorption after consuming low-zinc, low-phytate diets for several weeks. Such adaptation did not occur with higher phytate diets. Zinc absorption can be predicted from dietary zinc and phytate after allowing for dietary equilibration.


Subject(s)
Adaptation, Physiological , Nutritional Status , Phytic Acid/pharmacology , Zinc/administration & dosage , Zinc/pharmacokinetics , Adult , Biological Availability , Body Mass Index , Cross-Over Studies , Diet , Dose-Response Relationship, Drug , Female , Humans , Intestinal Absorption , Male , Middle Aged
13.
Am J Clin Nutr ; 86(2): 388-96, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17684210

ABSTRACT

BACKGROUND: An in vitro digestion and Caco-2 cell model may predict iron bioavailability to humans; however, direct comparisons are lacking. OBJECTIVE: The objective was to test the differences in iron bioavailability between 2 maize varieties and 2 bean varieties (white beans and colored beans) by comparing human, Caco-2, and algorithm results. DESIGN: Two randomized, 2 x 2 factorial experiments compared women's iron absorption from 2 maize varieties (ACR and TZB; n = 26) and 2 bean varieties (great northern and pinto; n = 13), each fed with and without ascorbic acid (AA) from orange juice. Nonheme iron bioavailability was determined from 2-wk retention of extrinsic radioiron tracers and was compared with Caco-2 cell and algorithm results from identical meals. RESULTS: Without AA supplementation, women absorbed only about 2% of the iron from the maize or bean meals. The results were unaffected by the variety of either maize or beans. Adding AA (15-20 molar ratios of AA:iron) roughly tripled the iron absorption (P < 0.0001) from all test meals. Although the Caco-2 model predicted a slightly improved bioavailability of iron from ACR maize than from TZB maize (P < 0.05), it accurately predicted relative iron absorption from the maize meals. However, the Caco-2 model inaccurately predicted both a considerable difference between bean varieties (P < 0.0001) and a strong interaction between bean varieties and enhancement by AA (P < 0.0001). The algorithm method was more qualitatively than quantitatively useful and requires further development to accurately predict the influence of polyphenols on iron absorption. CONCLUSIONS: Caco-2 predictions confirmed human iron absorption results for maize meals but not for bean meals, and algorithm predictions were only qualitatively predictive.


Subject(s)
Amino Acids/metabolism , Dietary Supplements , Fabaceae , Iron/metabolism , Zea mays , Adult , Algorithms , Beverages , Biological Availability , Body Mass Index , Cell Line, Tumor , Citrus , Erythrocytes/metabolism , Female , Humans , Intestinal Absorption , Male , Reproducibility of Results
14.
J Nutr ; 137(3): 620-7, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17311950

ABSTRACT

Commercial elemental iron powders (electrolytic and reduced iron), as well as heme iron supplements, were tested for efficacy in improving the iron status of women. In a randomized, double-blind trial, 51 women with moderate to low iron stores received daily for 12 wk: 1) placebo, 2) 5 mg iron as heme iron or 50 mg iron as 3) electrolytic iron, 4) reduced iron, or 5) FeSO(4). Treatments were provided in 2 capsules (heme carrier) and 3 wheat rolls (other iron sources). Differences in iron status, food nonheme iron absorption, and fecal properties were evaluated. Body iron, assessed from the serum transferrin receptor:ferritin ratio, increased significantly more in subjects administered FeSO(4) (127 +/- 29 mg; mean +/- SEM) and electrolytic (115 +/- 37 mg), but not the reduced (74 +/- 32 mg) or heme (65 +/- 26 mg) iron forms, compared with those given placebo (2 +/- 19 mg). Based on body iron determinations, retention of the added iron was estimated as 3.0, 2.7, 1.8, and 15.5%, in the 4 iron-treated groups, respectively. Iron treatments did not affect food iron absorption. The 50 mg/d iron treatments increased fecal iron and free radical-generating capacity in vitro, but did not affect fecal water cytotoxicity. In subjects administered FeSO(4), fecal water content was increased slightly but significantly more than in the placebo group. In conclusion, electrolytic iron was approximately 86% as efficacious as FeSO(4) for improving body iron, but the power of this study was insufficient to detect any efficacy of the reduced or heme iron within 12 wk. With modification, this methodology of testing higher levels of food fortification for several weeks in healthy women with low iron stores has the potential for economically assessing the efficiency of iron compounds to improve iron status.


Subject(s)
Iron Deficiencies , Iron, Dietary/administration & dosage , Iron/metabolism , Adult , Double-Blind Method , Electrolytes/administration & dosage , Electrolytes/pharmacokinetics , Feces/chemistry , Female , Ferritins/blood , Ferrous Compounds/administration & dosage , Ferrous Compounds/pharmacokinetics , Humans , Intestinal Absorption , Iron/blood , Iron, Dietary/pharmacokinetics , Middle Aged , Receptors, Transferrin/blood
15.
J Nutr ; 136(8): 2167-74, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16857836

ABSTRACT

Despite extensive use, information on the bioavailability of elemental iron powders to humans, as influenced by dose and other dietary constituents, is limited. Three experiments were conducted to assess the absorption of electrolytic iron powder relative to FeSO4, as affected by iron dose and by ascorbic or phytic acid. Iron absorption by 56 volunteers was measured from a farina cereal breakfast radiolabeled with 59FeSO4 or an electrolytic 55Fe powder irradiated by neutron activation. Absorption was determined from whole-body counting (59Fe) and blood isotope incorporation 2 wk later. Absorption of iron from the irradiated electrolytic powder was 5-15% that of FeSO4. Ascorbic acid (approximately 160 mg) enhanced iron absorption from FeSO4 by almost 4-fold but only doubled absorption from electrolytic iron (P for interaction < 0.01). Phytic acid from wheat bran inhibited iron absorption from FeSO4 and electrolytic iron by 73 and 50%, respectively (P for interaction, NS). Compared with 3 mg, a 20-mg dose reduced fractional absorption from FeSO4, but not electrolytic iron (P for interaction < 0.0001). Despite a much higher bioavailability (50% relative to FeSO4) of this same electrolytic iron when tested previously in a pig model, the bioavailability of the irradiated electrolytic iron was poor in humans. The diminished influence of ascorbic acid on the absorption of less soluble iron sources such as elemental iron powders may be an important consideration when choosing iron fortificants.


Subject(s)
Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Ferritins/blood , Ferrous Compounds/pharmacokinetics , Food, Fortified , Intestinal Absorption/drug effects , Iron, Dietary/pharmacokinetics , Phytic Acid/pharmacology , Adult , Biological Availability , Drug Interactions , Female , Ferrous Compounds/administration & dosage , Humans , Iron, Dietary/administration & dosage , Male , Middle Aged
16.
Am J Clin Nutr ; 84(1): 150-5, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16825689

ABSTRACT

BACKGROUND: Although hepcidin is proposed as a regulator of iron absorption, this has not been assessed in humans. OBJECTIVE: Our objective was to assess the relation between serum or urinary prohepcidin and iron absorption in healthy premenopausal women. DESIGN: The subjects were 28 healthy women aged 22-51 y with normal hemoglobin concentrations (120-152 g/L). Absorption of 0.5 mg Fe with 0.2 microCi 59Fe tracer, both as FeSO4, was measured by whole-body scintillation counting 13 d after oral administration. Fasting blood and urine samples were collected the day of and 16 wk after the absorption measurement. Serum and urinary prohepcidin concentrations were measured by an enzyme-linked immunosorbent assay by using an antibody against amino acid residues 28-47 of the proregion. RESULTS: Mean (+/-SD) iron absorption was 36 +/- 19% (range: 4-81%), and serum ferritin (geometric x) was 27 microg/L (range: 4-122 microg/L), as commonly observed in healthy premenopausal women. Serum prohepcidin was 196 microg/L (range: 99-376 microg/L) and, in contrast with urinary prohepcidin, was relatively consistent for the women between 0 and 16 wk. Serum prohepcidin correlated directly with serum ferritin (R2 = 0.28, P < 0.01) but was unrelated to 59Fe absorption, in contrast to serum ferritin (R2 = 0.33, P < 0.01). CONCLUSIONS: Serum prohepcidin concentrations were relatively stable within subjects and correlated with serum ferritin. However, unlike serum ferritin, neither serum nor urinary prohepcidin concentrations were related to iron absorption in healthy women.


Subject(s)
Antimicrobial Cationic Peptides/blood , Antimicrobial Cationic Peptides/urine , Intestinal Absorption/physiology , Iron, Dietary/pharmacokinetics , Protein Precursors/blood , Protein Precursors/urine , Administration, Oral , Adult , Antimicrobial Cationic Peptides/physiology , Biological Availability , Dietary Supplements , Enzyme-Linked Immunosorbent Assay , Female , Ferritins/blood , Hemoglobins/analysis , Hepcidins , Humans , Iron Compounds/blood , Iron Compounds/metabolism , Iron Compounds/pharmacokinetics , Iron Radioisotopes , Iron, Dietary/blood , Iron, Dietary/metabolism , Middle Aged , Premenopause , Scintillation Counting
17.
Am J Clin Nutr ; 82(3): 589-97, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16155272

ABSTRACT

BACKGROUND: Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. OBJECTIVES: We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and to compare the serosal transfer of heme and nonheme iron, which should not differ if the 2 forms have entered a common mucosal iron pool. DESIGN: Whole-gut lavage and whole-body counting were used to measure the initial uptake (8 h) and retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg). Two experiments tested basal meals with low iron bioavailability and 360 mg Ca (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12). RESULTS: Added calcium reduced the initial uptake of heme iron by 20%, from 49% to approximately 40% from both meals (P = 0.02), and reduced the total iron absorbed from the low- and high-bioavailability meals by approximately 25% [from 0.033 to 0.025 mg (P = 0.06) and from 0.55 to 0.40 mg (P < 0.01), respectively]. Calcium did not affect the serosal transfer of either form of iron. CONCLUSIONS: Calcium supplementation reduced heme and total iron without significantly affecting nonheme-iron absorption, regardless of meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of heme iron. Differences in serosal transfer indicate that heme and nonheme iron did not enter a common absorptive pool within 8 h after a meal.


Subject(s)
Calcium, Dietary/pharmacology , Erythrocytes/metabolism , Heme/pharmacokinetics , Intestinal Absorption/drug effects , Intestinal Mucosa/metabolism , Iron, Dietary/pharmacokinetics , Administration, Oral , Adult , Aged , Animals , Biological Availability , Calcium, Dietary/classification , Cross-Over Studies , Female , Ferritins/blood , Humans , Iron Radioisotopes , Male , Middle Aged , Therapeutic Irrigation
19.
Int J Vitam Nutr Res ; 75(6): 375-84, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16711471

ABSTRACT

Iron deficiency, a global health problem, impairs reproductive performance, cognitive development, and work capacity. One proposed strategy to address this problem is the improvement of dietary iron bioavailability. Knowledge of the molecular mechanisms of iron absorption is growing rapidly, with identification of mucosal iron transport and regulatory proteins. Both body iron status and dietary characteristics substantially influence iron absorption, with minimal interaction between these two factors. Iron availability can be regarded mainly as a characteristic of the diet, but comparisons between human studies of iron availability for absorption require normalization for the iron status of the subjects. The dietary characteristics that enhance or inhibit iron absorption from foods have been sensitively and quantitatively determined in human studies employing iron isotopes. People with low iron status can substantially increase their iron absorption from diets with moderate to high availability. But while iron supplementation and fortification trials can effectively increase blood indices of iron status, improvements in dietary availability alone have had minimal influence on such indices within several weeks or months. Plentiful, varied diets are the ultimate resolution to iron deficiency. Without these, more modest food-based approaches to human iron deficiency likely will need to be augmented by dietary iron fortification.


Subject(s)
Intestinal Absorption/physiology , Iron/pharmacokinetics , Biological Availability , Diet , Female , Humans , Iron/metabolism , Male
20.
J Clin Endocrinol Metab ; 90(1): 181-9, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15483071

ABSTRACT

In a controlled feeding study, the effects of substituting 25 g soy protein for meat on calcium retention and bone biomarkers were determined. Postmenopausal women (n = 13) ate two diets that were similar, except that, in one diet, 25 g high-isoflavone soy protein (SOY) was substituted for an equivalent amount of meat protein (control diet), for 7 wk each in a randomized crossover design. After 3 wk of equilibration, calcium retention was measured by labeling the 2-d menu with (47)Ca, followed by whole-body counting for 28 d. Urinary calcium and renal acid excretion were measured at wk 3, 5, and 7. Biomarkers of bone and cardiovascular health were measured at the beginning and end of each diet. Calcium was similarly retained during the control and SOY diets (d 28, percent dose, mean +/- pooled sd: 14.1 and 14.0 +/- 1.6, respectively). Despite a 15-20% lower renal acid excretion during the SOY diet, urinary calcium loss was unaffected by diet. Diet also did not affect any of the indicators of bone or cardiovascular health. Substitution of 25 g high isoflavone soy protein for meat, in the presence of typical calcium intakes, did not improve or impair calcium retention or indicators of bone and cardiovascular health in postmenopausal women.


Subject(s)
Bone and Bones/metabolism , Calcium/metabolism , Postmenopause/metabolism , Soybean Proteins/administration & dosage , Aged , Cross-Over Studies , Female , Hemostasis , Homocysteine/blood , Humans , Isoflavones/urine , Lipids/blood , Meat , Middle Aged
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