ABSTRACT
Purpose: To compare and evaluate 2 methods of inventory management in automated dispensing cabinets (ADCs). Methods: Ten profiled ADCs had 2 inventory management models implemented over 2 months. Implementation of the models on each ADC involved adjustment of par levels (desired accessible quantities of medication) and removal of medications not used in the past 90 days or more. The par levels of 5 ADCs were adjusted using a formula developed based on the economic order quantity model. The par levels of the other 5 ADCs were adjusted using a formula based on historical average daily usage. The study endpoints include stock out rate, vend:fill ratio, quantity of expired medications, and inventory carrying cost. Results: The total of number of medications stocked in the 10 ADCs was reduced from 3035 in a 2-month pre-implementation period to 2932 in a 2-month post-implementation period yielding a reduction of inventory carrying cost by $11 011. The mean stock out rate in both study groups increased and vend:fill ratio decreased after implementation. The quantity of expired medications increased in the modified economic order quantity formula inventory management model and decreased in the average daily usage inventory management model. Conclusion: The implementation of 2 inventory management models on ADCs had a negative impact on stock out rate and vend:fill ratio, a mixed impact on quantity of expired medications, and a positive impact on inventory carrying cost reduction.
ABSTRACT
The International Union of Pure and Applied Chemistry (IUPAC) has a long tradition of supporting the compilation of chemical data and their evaluation through direct projects, nomenclature and terminology work, and partnerships with international scientific bodies, government agencies and other organizations. The IUPAC Interdivisional Subcommittee on Critical Evaluation of Data (ISCED) has been established to provide guidance on issues related to the evaluation of chemical data. In this first report we define the general principles of the evaluation of scientific data and describe best practices and approaches to data evaluation in chemistry.
ABSTRACT
Protein turnover maintains the proteome's functional integrity. Here, protein turnover efficiency over time in wild-type Caenorhabditis elegans was assessed using inverse [15N]-pulse labeling up to 7 days after the egg-laying phase at 20 °C. Isotopic analysis of some abundant proteins was executed favoring data quality over quantity for mathematical modeling. Surprisingly, isotopic enrichment over time reached an upper limit showing an apparent cessation of protein renewal well before death, with protein fractions inaccessible to turnover ranging from 14 to 83%. For life span modulation, worms were raised at different temperatures after egg laying. Mathematical modeling of isotopic enrichment points either to a slowdown of protein turnover or to an increasing protein fraction resistant to turnover with time. Most notably, the estimated time points of protein turnover cessation from our mathematical model were highly correlated with the observed median life span. Thrashing and pumping rates over time were linearly correlated with isotopic enrichment, therefore linking protein/tracer intake to protein turnover rate and protein life span. If confirmed, life span extension is possible by optimizing protein turnover rate through modulating protein intake in C. elegans and possibly other organisms. While proteome maintenance benefits from a high protein turnover rate, protein turnover is fundamentally energy-intensive, where oxidative stress contributes to damage that it is supposed to repair.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Proteome/genetics , Proteome/metabolism , Longevity , Aging/metabolism , EatingABSTRACT
Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.
Subject(s)
Diet, Ketogenic , Alzheimer Disease/diet therapy , Animals , Consultants , Diet, Ketogenic/adverse effects , Epilepsy/diet therapy , Glaucoma/diet therapy , Humans , Parkinson Disease/diet therapy , PharmacistsABSTRACT
BACKGROUND: Calcium inhibits and ascorbic acid (AA) enhances iron absorption from iron-fortified foods. Absorption efficiency depends on iron status, although the interaction is unclear. OBJECTIVE: We investigated the ability of AA to overcome calcium-induced inhibition of iron absorption in children differing in iron status. METHODS: The effect of calcium (0, 100, and 200 mg/test meal) on iron absorption in the absence and presence of AA (0, 42.5, and 85 mg/test meal) from a casein/whey-based drink fortified with ferrous sulfate was assessed in a series of randomized crossover studies both in iron-replete (IR) Indian schoolchildren and in children with iron deficiency anemia (IDA) (6-11 y; n = 14-16/group) by using stable isotopes. RESULTS: In the absence of calcium and AA, iron absorption from the casein/whey-based drink was 20% lower in IR children than in children with IDA. The addition of calcium reduced mean iron absorption by 18-27%, with the effect being stronger for high added calcium (P < 0.01). AA at a 2:1 or 4:1 molar ratio enhanced iron absorption by a factor of 2-4 and greatly overcompensated for the inhibitory effect of calcium on iron absorption in a dose-dependent manner (P < 0.001). The dose-response effect tended to be stronger (P < 0.1) in the IDA group, and iron status was of far less influence on iron absorption than the enhancing effect of AA. CONCLUSION: When adding AA to iron-fortified milk products, care should be taken not to provide absorbable iron in excess of needs.
Subject(s)
Ascorbic Acid/pharmacokinetics , Beverages/analysis , Calcium/pharmacokinetics , Caseins/chemistry , Iron/metabolism , Milk Proteins/chemistry , Ascorbic Acid/chemistry , Child , Child Nutritional Physiological Phenomena , Cross-Over Studies , Dietary Supplements , Drug Interactions , Female , Humans , India , Iron/pharmacokinetics , Male , Whey ProteinsABSTRACT
Subtle variations in the isotopic composition of elements carry unique information about physical and chemical processes in nature and are now exploited widely in diverse areas of research. Reliable measurement of natural isotope abundance variations is among the biggest challenges in inorganic mass spectrometry as they are highly sensitive to methodological bias. For decades, double spiking of the sample with a mix of two stable isotopes has been considered the reference technique for measuring such variations both by multicollector-inductively coupled plasma mass spectrometry (MC-ICPMS) and multicollector-thermal ionization mass spectrometry (MC-TIMS). However, this technique can only be applied to elements having at least four stable isotopes. Here we present a novel approach that requires measurement of three isotope signals only and which is more robust than the conventional double spiking technique. This became possible by gravimetric mixing of the sample with an isotopic spike in different proportions and by applying principles of isotope dilution for data analysis (GS-IDA). The potential and principle use of the technique is demonstrated for Mg in human urine using MC-TIMS for isotopic analysis. Mg is an element inaccessible to double spiking methods as it consists of three stable isotopes only and shows great potential for metabolically induced isotope effects waiting to be explored.
Subject(s)
Indicator Dilution Techniques , Magnesium/urine , Mass Spectrometry/methods , Humans , Isotopes/analysis , Isotopes/urine , Magnesium/analysis , Sensitivity and SpecificityABSTRACT
Persistent impairments in the regulation of intestinal iron absorption result in iron deficiency or iron accumulation in the long term. Diagnosis remains difficult unless pathological symptoms develop as iron absorption varies strongly between meals and days. Variations in the natural iron isotopic composition of whole blood have recently been suggested as a novel parameter to assess long-term differences in intestinal absorption efficiency between individuals. In this study, baseline blood samples collected in two previous conventional iron absorption studies in Swiss and Thai women using stable isotope tracers were reanalyzed by multicollector inductively coupled plasma mass spectrometry. The natural iron isotopic compositions obtained were compared with fractional absorption from the test meals observed in these earlier trials. Correlations of natural blood iron isotopic composition and fractional absorption from the test meals were found to be highly significant in both cohorts (for Swiss women, r = 0.40, P = 0.01, n = 38; for Thai women, r = 0.57, P < 0.01, n = 24), with the blood of both ethnicities clearly differing in iron isotopic composition (P < 0.001). Combining the findings of this study and those of recent animal and human studies confirms that blood iron isotopic patterns may serve as a novel compound biomarker of iron metabolism to assess impairments in regulation of intestinal iron absorption in individuals or population groups.
Subject(s)
Intestinal Absorption , Iron Isotopes/blood , Iron, Dietary/metabolism , Female , Humans , Time Factors , Young AdultABSTRACT
PURPOSE: The main purpose of this study was to establish bioavailability data in humans for the new (Fe) fortification compound ferrous ammonium phosphate (FAP), which was specially developed for fortification of difficult-to-fortify foods where soluble Fe compounds cannot be used due to their negative impact on product stability. METHODS: A double-blind, randomized clinical trial with cross-over design was conducted to obtain bioavailability data for FAP in humans. In this trial, Fe absorption from FAP-fortified full-cream milk powder was compared to that from ferric pyrophosphate (FPP) and ferrous sulfate. Fe absorption was determined in 38 young women using the erythrocyte incorporation dual stable isotope technique (57Fe, 58Fe). RESULTS: Geometric mean Fe absorption from ferrous sulfate, FAP and FPP was 10.4, 7.4 and 3.3 %, respectively. Fe from FAP was significantly better absorbed from milk than Fe from FPP (p < 0.0001). Fe absorption from FAP was significantly lower than Fe absorption from ferrous sulfate, which was used as water-soluble reference compound (p = 0.0002). Absorption ratios of FAP and FPP relative to ferrous sulfate as a measure of relative bioavailability were 0.71 and 0.32, respectively. CONCLUSIONS: The results of the present studies show that replacing FPP with FAP in full-cream milk could significantly improve iron bioavailability.
Subject(s)
Beverages , Dairy Products , Ferrous Compounds/metabolism , Food, Fortified , Iron, Dietary/administration & dosage , Phosphates/metabolism , Adult , Cross-Over Studies , Diphosphates/chemistry , Diphosphates/metabolism , Double-Blind Method , Erythrocytes/metabolism , Female , Ferrous Compounds/chemistry , Food, Preserved , Humans , Intestinal Absorption , Iron/chemistry , Iron/metabolism , Iron Isotopes , Iron, Dietary/metabolism , Nutritive Value , Phosphates/chemistry , Solubility , Young AdultABSTRACT
We recently showed in an animal model that iron isotopic composition varies substantially between different organs. For instance, iron in ferritin-rich organs--such as the major storage tissues liver, spleen, and bone marrow--contain a larger fraction of the heavy iron isotopes compared with other tissues, including blood. As a consequence, partitioning of body iron into red blood cells and storage compartments should be reflected in the isotopic pattern of blood iron. To confirm this hypothesis, we monitored blood iron isotope patterns in iron-overloaded subjects undergoing phlebotomy treatment by multicollector inductively coupled plasma mass spectrometry. We found that bloodletting and consequential replacement of lost blood iron by storage iron led to a substantial increase of the heavy isotope fraction in the blood. The progress of iron depletion therapy and blood loss was quantitatively traceable by isotopic shifts of as much as +1 in δ((56)Fe). These results show that--together with iron absorption efficiency--partitioning of iron between blood and iron storage tissues is an important determinant of blood iron isotopic patterns, which could make blood iron isotopic composition the first composite measure of iron metabolism in humans.
Subject(s)
Iron/blood , Iron/metabolism , Adult , Female , Humans , Iron Isotopes/blood , Iron Isotopes/metabolism , Male , Mass Spectrometry , Middle Aged , PhlebotomyABSTRACT
Despite the importance of stating the measurement uncertainty in chemical analysis, concepts are still not widely applied by the broader scientific community. The Guide to the expression of uncertainty in measurement approves the use of both the partial derivative approach and the Monte Carlo approach. There are two limitations to the partial derivative approach. Firstly, it involves the computation of first-order derivatives of each component of the output quantity. This requires some mathematical skills and can be tedious if the mathematical model is complex. Secondly, it is not able to predict the probability distribution of the output quantity accurately if the input quantities are not normally distributed. Knowledge of the probability distribution is essential to determine the coverage interval. The Monte Carlo approach performs random sampling from probability distributions of the input quantities; hence, there is no need to compute first-order derivatives. In addition, it gives the probability density function of the output quantity as the end result, from which the coverage interval can be determined. Here we demonstrate how the Monte Carlo approach can be easily implemented to estimate measurement uncertainty using a standard spreadsheet software program such as Microsoft Excel. It is our aim to provide the analytical community with a tool to estimate measurement uncertainty using software that is already widely available and that is so simple to apply that it can even be used by students with basic computer skills and minimal mathematical knowledge.
Subject(s)
Uncertainty , Monte Carlo Method , Probability , SoftwareABSTRACT
Low iron absorption from common beans might contribute to iron deficiency in countries where beans are a staple food. High levels of phytic acid (PA) and polyphenols (PP) inhibit iron absorption; however, the effect of bean PP on iron absorption in humans has not been demonstrated and, with respect to variety selection, the relative importance of PP and PA is unclear. To evaluate the influence of bean PP relative to PA on iron absorption in humans, 6 stable iron isotope absorption studies were conducted in women (16 or 17 per study). Bean PP (20, 50, and 200 mg) were added in studies 1-3 as red bean hulls to a bread meal. Studies 4- 6 investigated the influence on iron absorption of PP removal and dephytinization of whole red bean porridge and PP removal from dephytinized porridge. Iron absorption was lowered by 14% with 50 mg PP (P < 0.05) and by 45% with 200 mg PP (P < 0.001). The mean iron absorption from whole bean porridge was 2.5%. PP and PA removal increased absorption 2.6-fold (P < 0.001) and removal of PP from dephytinized porridge doubled absorption (P < 0.001). Between-study comparisons indicated that dephytinization did not increase iron absorption in the presence of PP, but in their absence, absorption increased 3.4-fold (P < 0.001). These data suggest that in countries where beans are a staple food, PP and PA concentrations should be considered when selecting bean varieties for human consumption. Lowering only one inhibitor will have a modest influence on iron absorption.
Subject(s)
Diet , Fabaceae/chemistry , Flavonoids/administration & dosage , Intestinal Absorption , Iron, Dietary/metabolism , Phenols/administration & dosage , Phytic Acid/administration & dosage , Seeds/chemistry , Adolescent , Adult , Bread/analysis , Cross-Over Studies , Female , Flavonoids/analysis , Food Handling/methods , Humans , Iron Isotopes , Middle Aged , Phenols/analysis , Phytic Acid/analysis , Polyphenols , Young AdultABSTRACT
Ferritin is nature's predominant iron storage protein. The molecule consists of a hollow protein shell composed of 24 subunits which is capable of storing up to 4500 iron atoms per molecule. Recently, this protein has been identified as a target molecule for increasing iron content in plant staple foods in order to combat dietary iron deficiency, a major public health problem in developing countries. Here, we present a novel technique for quantification of ferritin-bound iron in edible plant seeds using species-specific isotope dilution mass spectrometry (IDMS) by means of a biosynthetically produced (57)Fe-labeled ferritin spike and negative thermal ionization mass spectrometry (NTIMS). Native plant ferritin and added spike ferritin were extracted in 20 mM Tris buffer (pH 7.4) and separated by anion exchange chromatography (DEAE Sepharose), followed by isotopic analysis by thermal ionization mass spectrometry. The chosen IDMS approach was critically evaluated by assessing the (i) efficiency of analyte extraction, (ii) identical behavior of spike and analyte, and (iii) potential iron isotope exchange with natural iron. Repeatabilities that can be achieved are on the order of <5% RSD for quintuplicate analyses at an absolute detection limit of 60 ng of ferritin-bound iron for plant seeds. Studies in six different legumes revealed ferritin-iron contents ranging from 15% of total iron in red kidney beans up to 69% in lentils.
Subject(s)
Ferritins/analysis , Iron/analysis , Mass Spectrometry/methods , Plants, Edible/chemistry , Seeds/chemistry , Ferritins/isolation & purification , Iron Isotopes/analysisABSTRACT
OBJECTIVE: The aim of this study was to develop and validate a high-pressure liquid chromatography (HPLC) method for assessing vitamin D status as 25-hydroxyvitamin D(2) (S-25OHD(2)) and 25-hydroxyvitamin D(3) (S-25OHD(3)) in serum. MATERIAL AND METHODS: We assessed the within- and between-subject variation of vitamin D status in serum samples from four different dietary intervention studies in which subjects (n = 92) were supplemented with different doses of vitamin D(3) (5-12 microg/day) and for different durations (4-20 months). RESULTS: The HPLC method was applicable for 4.0-200 nmol S-25OHD/L, while the within-day and between-days variations were 3.8 % and 5.7 %, respectively. There was a concentration-dependent difference between results obtained by a commercial radioimmunoassay and results from the HPLC method of -5 to 20 nmol 25OHD/L in the range 10-100 nmol 25OHD/L. The between-subject variation estimated in each of the four human intervention studies did not differ significantly (p = 0.55). Hence, the pooled standard deviation was 15.3 nmol 25OHD(3)/L. In the studies with 6-8 samplings during 7-20 months of supplementation, the within-subject variation was 3.9-7.2 nmol 25OHD(3)/L, while vitamin D status was in the range 47-120 nmol/L. CONCLUSIONS: The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D(3). The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin D status.
Subject(s)
25-Hydroxyvitamin D 2/blood , Calcifediol/administration & dosage , Calcifediol/blood , Chromatography, High Pressure Liquid/methods , Humans , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: A highly soluble iron-casein complex has been developed for food fortification purposes with the aim to provide high iron bioavailability. OBJECTIVE: We aimed to determine the iron bioavailability of the iron-casein complex relative to that of ferrous sulfate (control) when given with whole milk in healthy young women. METHODS: A randomized comparator-controlled trial with a crossover design was conducted using the erythrocyte incorporation dual stable isotope (57Fe, 58Fe) technique. Iron absorption from the iron-casein complex was compared with that from ferrous sulfate in 21 healthy women aged 20-38 y with normal iron status. RESULTS: Fractional iron absorption (geometric mean; -SD, +SD) from the iron-casein complex (3.4%; 1.4%, 5.4%) and from ferrous sulfate (3.9%; 1.7%, 6.1%) were not statistically different (P > 0.05). The relative bioavailability value of the iron-casein complex to ferrous sulfate was determined to be 0.87 (-1 SD, +1 SD: -0.90, +2.64). CONCLUSIONS: The iron-casein complex has iron bioavailability comparable to that of ferrous sulfate in healthy young women. This trial was registered at www.anzctr.org.au as ACTRN12615000690550.
Subject(s)
Caseins/metabolism , Ferrous Compounds/metabolism , Food Additives/metabolism , Iron/metabolism , Milk/metabolism , Adult , Animals , Biological Availability , Female , Food, Fortified/analysis , Humans , Iron Isotopes/metabolism , Milk/chemistry , Young AdultABSTRACT
Biofortification of staple foods with iron in the form of ferritin-iron is a promising approach to fighting iron-deficiency anemia in developing countries. However, contradictory results regarding iron bioavailability to humans from ferritin are not yet fully clarified. Furthermore, the question has been raised whether ferritin can potentially survive gastric passage intact and be absorbed via a ferritin-specific uptake mechanism. We studied changes of ferritin-iron and protein during cooking and in vitro gastric digestion. Water soluble, native ferritin-iron, measured in different legumes, represented 18% (soybeans) up to maximally 42% (peas) of total seed iron. Ferritin-iron was no longer detectable after boiling the legumes for 50 min in excess water. When the same cooking treatment was applied to recombinant bean ferritin propagated in Escherichia coli, some ferritin-iron remained measurable. During in vitro gastric digestion of recombinant bean ferritin and red kidney bean extract, ferritin-iron was fully released from the protein and dissolved at pH 2. Stability tests at varying pH at 37 degrees C showed that the release of ferritin-iron starts at pH 5 and is complete at pH 2. We concluded that ferritin-iron is efficiently released from the ferritin molecule during cooking and at gastric pH and that it should be absorbed as efficiently as all other nonheme iron in food.
Subject(s)
Digestion , Ferritins/metabolism , Hot Temperature , Iron/metabolism , Animals , Biological Availability , Drug Stability , Edetic Acid/pharmacology , Escherichia coli/genetics , Fabaceae/chemistry , Ferritins/genetics , Food, Fortified , Gastric Acid/metabolism , Gastric Mucosa/enzymology , Gene Expression , Hydrogen-Ion Concentration , In Vitro Techniques , Iron/analysis , Kinetics , Pepsin A/metabolism , Phaseolus/chemistry , Recombinant Proteins/metabolism , SwineABSTRACT
Ferritin is the major iron storage protein in the biosphere. Iron stores of an organism are commonly assessed by measuring the concentration of the protein shell of the molecule in fluids and tissues. The amount of ferritin-bound iron, the more desirable information, still remains inaccessible owing to the lack of suitable techniques. Iron saturation of ferritin is highly variable, with a maximum capacity of 4,500 iron atoms per molecule. This study describes the direct isotopic labeling of a complex metalloprotein in vivo by biosynthesis, in order to measure ferritin-bound iron by isotope dilution mass spectrometry. [(57)Fe]ferritin was produced by cloning and overexpressing the Phaseolus vulgaris ferritin gene pfe in Escherichia coli in the presence of (57)FeCl(2). Recombinant ferritin was purified in a fully assembled form and contained approximately 1,000 iron atoms per molecule at an isotopic enrichment of more than 95% (57)Fe. We did not find any evidence of species conversion of the isotopic label for at least 5 months of storage at -20 degrees C. Transfer efficiency of enriched iron into [(57)Fe]ferritin of 20% was sufficient to be economically feasible. Negligible amounts of non-ferritin-bound iron in the purified [(57)Fe]ferritin solution allows for use of this spike for quantification of ferritin-bound iron by isotope dilution mass spectrometry.
Subject(s)
Escherichia coli/metabolism , Ferritins/analysis , Ferritins/isolation & purification , Gene Expression , Phaseolus/metabolism , Chromatography, Gel , Escherichia coli/genetics , Fabaceae/metabolism , Ferritins/biosynthesis , Ferritins/genetics , Iron Isotopes/chemistry , Phaseolus/genetics , Plant Extracts/metabolism , Recombinant Proteins/analysis , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purificationABSTRACT
UNLABELLED: A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.
Subject(s)
Bone Density/drug effects , Diphosphonates/pharmacology , Postmenopause/metabolism , Postmenopause/urine , Aged , Biomarkers , Bone Diseases, Metabolic/drug therapy , Calcium Radioisotopes/urine , Diphosphonates/therapeutic use , Etidronic Acid/analogs & derivatives , Etidronic Acid/pharmacology , Etidronic Acid/therapeutic use , Female , Humans , Kinetics , Osteoporosis, Postmenopausal/drug therapy , Risedronic Acid , Sensitivity and SpecificityABSTRACT
BACKGROUND: Anemia and iron deficiency are significant public health problems in India, particularly among women and children. Recent figures suggest that nearly 50% of young Indian women are anemic. OBJECTIVES: Few studies have comprehensively assessed etiologic factors contributing to anemia and iron deficiency in India. Hence, this study assessed the relative importance of various factors contributing to these problems in young women of low socioeconomic status in Bangalore, India. METHODS: A random sample of 100 nonpregnant, nonlactating women 18 to 35 years of age, selected from among 511 women living in a poor urban settlement, participated in this study. Data were obtained on demography, socioeconomic status, anthropometry, three-day dietary intake, blood hemoglobin, hemoglobinopathies, serum ferritin, serum C-reactive protein, and stool parasites. RESULTS: The prevalence rates of anemia and iron deficiency were 39% and 62%, respectively; 95% of the anemic women were iron deficient. The mean dietary iron intake was 9.5 mg per day, predominantly from the consumption of cereals, pulses, and vegetables (77%). The estimated bioavailability of nonheme iron in this diet was 2.8%. Dietary intakes were suboptimal for several nutrients. Blood hemoglobin was significantly correlated with dietary intake of fat, riboflavin, milk and yogurt, and coffee. Serum ferritin was significantly correlated with intake of niacin, vitamin B12, and selenium. Parasitic infestation was low. CONCLUSIONS: An inadequate intake of dietary iron, its poor bioavailability, and concurrent inadequate intake of dietary micronutrients appear to be the primary factors responsible for the high prevalence of anemia and iron deficiency in this population.
Subject(s)
Anemia, Iron-Deficiency/etiology , Diet , Iron Deficiencies , Iron, Dietary/administration & dosage , Social Class , Adolescent , Adult , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/epidemiology , Biological Availability , Comorbidity , Female , Hemoglobins/analysis , Humans , India/epidemiology , Iron/blood , Iron, Dietary/pharmacokinetics , Parasitic Diseases/epidemiology , Risk Factors , Seroepidemiologic Studies , Socioeconomic FactorsABSTRACT
BACKGROUND: Although ferric pyrophosphate is a promising compound for iron fortification of foods, few data are available on the effect of food matrices, processing, and ascorbic acid on its bioavailability. OBJECTIVE: We compared the relative bioavailability (RBV) of ferrous sulfate in an experimental form of micronized dispersible ferric pyrophosphate (MDFP) in a wheat-milk infant cereal given with and without ascorbic acid with the RBV of MDFP from a processed and unprocessed rice meal. DESIGN: A crossover design was used to measure iron absorption in young women (n = 26) from test meals fortified with isotopically labeled [57Fe]-MDFP and [58Fe]-ferrous sulfate, based on erythrocyte incorporation of stable isotope labels 14 d later. RESULTS: Geometric mean iron absorption from the wheat-based meal fortified with MDFP was 2.0% and that from the meal fortified with ferrous sulfate was 3.2% (RBV = 62). The addition of ascorbic acid at a molar ratio of 4:1 to iron increased iron absorption from MDFP to 5.8% and that from ferrous sulfate to 14.8% (RBV = 39). In the rice meals, mean iron absorption from MDFP added to the rice at the time of feeding was 1.7%, and that from ferrous sulfate was 11.6% (RBV = 15). The mean iron absorption from MDFP extruded into artificial rice grains was 3.0% and that from ferrous sulfate in unprocessed rice was 12.6% (RBV = 24). Sixteen of 26 subjects were iron deficient. Iron status was a highly significant predictor of the RBV of MDFP (P < 0.001). CONCLUSION: RBV of the experimental MDFP varied markedly with food matrix and iron status. Assigning a single RBV value to poorly soluble compounds may be of limited value in evaluating their suitability for food fortification.
Subject(s)
Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Diphosphates/pharmacokinetics , Ferrous Compounds/pharmacokinetics , Food Handling/methods , Food , Iron/pharmacokinetics , Absorption , Adult , Biological Availability , Cross-Over Studies , Diphosphates/metabolism , Female , Ferritins/blood , Ferrous Compounds/metabolism , Food, Fortified , Humans , Intestinal Absorption/drug effects , Iron/metabolism , Iron Isotopes , Nutritional Status , Oryza/chemistry , Triticum/chemistryABSTRACT
BACKGROUND: Phytic acid is a strong inhibitor of iron absorption from fortified foods. In adults, this inhibitory effect can be overcome by adding ascorbic acid with the iron fortificant or by using a "protected" iron compound such as NaFeEDTA. In addition, the use of NaFeEDTA as an iron fortificant has been reported to increase zinc absorption in adult women. No information is available on iron bioavailability from NaFeEDTA or the influence of NaFeEDTA on minerals and trace elements in infants. OBJECTIVE: We aimed to compare iron bioavailability from a complementary food based on wheat and soy fortified with either NaFeEDTA or ferrous sulfate plus ascorbic acid. The apparent absorption of zinc, copper, calcium, and magnesium was evaluated in parallel. DESIGN: Stable-isotope techniques were used in a crossover design to evaluate erythrocyte incorporation of iron 14 d after administration of labeled test meals and the apparent absorption of zinc, copper, calcium, and magnesium on the basis of fecal monitoring in 11 infants. RESULTS: Geometric mean erythrocyte incorporation of iron was 3.7% (NaFeEDTA) and 4.9% (ferrous sulfate plus ascorbic acid) (P = 0.08). No significant differences in the apparent absorption of zinc, copper, calcium, or magnesium were observed between test meals (n = 10). CONCLUSIONS: Iron bioavailability from a high-phytate, cereal-based complementary food fortified with either NaFeEDTA or ferrous sulfate plus ascorbic acid was not significantly different. NaFeEDTA did not influence the apparent absorption of zinc, copper, calcium, or magnesium. NaFeEDTA does not provide any nutritional benefit compared with the combination of a highly bioavailable iron compound and ascorbic acid.