A comparison of the bioavailability of ferrous fumarate and ferrous sulfate in non-anemic Mexican women and children consuming a sweetened maize and milk drink.

BACKGROUND/OBJECTIVES: Ferrous fumarate is recommended for the fortification of complementary foods based on similar iron absorption to ferrous sulfate in adults. Two recent studies in young children have reported that it is only 30% as well absorbed as ferrous sulfate. The objective of this study was to compare iron absorption from ferrous fumarate and ferrous sulfate in infants, young children and mothers. SUBJECTS/METHODS: Non-anemic Mexican infants (6-24 months), young children (2-5 years) and adult women were randomly assigned to receive either 4 mg Fe (women) or 2.5 mg Fe (infants and young children) as either [(57)Fe]-ferrous fumarate or [(58)Fe]-ferrous sulfate added to a sweetened drink based on degermed maize flour and milk powder. Iron absorption was calculated based on incorporation of isotopes into erythrocytes after 14 days. RESULTS: Within each population group, no significant differences (P > 0.05) in iron absorption were found between ferrous fumarate and ferrous sulfate. Mean iron absorption from ferrous fumarate vs ferrous sulfate was 17.5 vs 20.5% in women (relative bioavailability (RBV) =86), 7.0 vs 7.2% in infants (RBV = 97) and 6.3 vs 5.9% in young children (RBV = 106). CONCLUSIONS: Ferrous fumarate is as well absorbed as ferrous sulfate in non-anemic, iron sufficient infants and young children, and can be recommended as a useful fortification compound for complementary foods designed to prevent iron deficiency. Further studies are needed to clarify its usefulness in foods designed to treat iron deficiency.

Oxalic acid does not influence nonhaem iron absorption in humans: a comparison of kale and spinach meals.

OBJECTIVE: To evaluate the influence of oxalic acid (OA) on nonhaem iron absorption in humans. DESIGN: Two randomized crossover stable iron isotope absorption studies. SETTING: Zurich, Switzerland. SUBJECTS: Sixteen apparently healthy women (18-45 years, <60 kg body weight), recruited by poster advertizing from the staff and student populations of the ETH, University and University Hospital of Zurich, Switzerland. Thirteen subjects completed both studies. METHODS: Iron absorption was measured based on erythrocyte incorporation of (57)Fe or (58)Fe 14 days after the administration of labelled meals. In study I, test meals consisted of two wheat bread rolls (100 g) and either 150 g spinach with a native OA content of 1.27 g (reference meal) or 150 g kale with a native OA content of 0.01 g. In study II, 150 g kale given with a potassium oxalate drink to obtain a total OA content of 1.27 g was compared to the spinach meal. RESULTS: After normalization for the spinach reference meal absorption, geometric mean iron absorption from wheat bread rolls with kale (10.7%) did not differ significantly from wheat rolls with kale plus 1.26 g OA added as potassium oxalate (11.5%, P=0.86). Spinach was significantly higher in calcium and polyphenols than kale and absorption from the spinach meal was 24% lower compared to the kale meal without added OA, but the difference did not reach statistical significance (P>0.16). CONCLUSION: Potassium oxalate did not influence iron absorption in humans from a kale meal and our findings strongly suggest that OA in fruits and vegetables is of minor relevance in iron nutrition.

Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism.

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

Urinary excretion of an intravenous 26Mg dose as an indicator of marginal magnesium deficiency in adults.

BACKGROUND: Measurement of magnesium (Mg) status is problematic because tissue Mg deficiency can be present without low serum Mg concentrations. OBJECTIVE: To evaluate a modified version of the Mg retention test using stable isotopes for the assessment of Mg status in general, and the detection of marginal Mg deficiency in particular. DESIGN: A modified version of the Mg retention test using a small dose of (26)Mg was evaluated for assessment of Mg status in 22 healthy subjects. Muscle Mg concentration was used as reference for Mg status. A muscle biopsy was taken from the lateral portion of the quadriceps muscle from each subject. After 2 to 4 weeks, 11 mg of (26)Mg (as MgCl(2) in 14 ml water) were injected i.v. over a period of 10 min and all urine was collected for the following 24 h. Excretion of the isotopic label was expressed as percentage of the administered dose excreted in urine within 24 h. RESULTS: Mean +/- s.d. Mg concentration in muscle was 3.85 +/- 0.17 mmol/100 g fat-free dried solids. Mean +/- s.d. excretion of the injected dose within 24 h was 7.9 +/- 2.1%. No correlation was found between muscle Mg concentration and excretion of the isotopic label (r (2 ) = 0.061, P = 0.27). CONCLUSIONS: In this study, urinary excretion of an intravenous Mg tracer was not influenced by muscle Mg concentration and its usefulness for the detection of marginal Mg deficiency could therefore not be demonstrated. SPONSORSHIP: Swiss Foundation for Nutrition Research and Swiss Federal Institute of Technology, Zurich, Switzerland.

Iron absorption by human subjects from different iron fortification compounds added to Thai fish sauce.

OBJECTIVES: (a) To measure iron absorption by human subjects from citric acid stabilized fish sauce fortified with ferrous sulfate, ferric ammonium citrate or ferrous lactate and (b) to identify the effect of added citric acid (3 g/l) on iron absorption from ferrous sulfate fortified fish sauce. DESIGN: Iron absorption from the intrinsically labeled compounds was determined via erythrocyte incorporation of isotopic labels ((57)Fe and (58)Fe) using a randomized crossover design. In three separate absorption studies, 10 adult women each consumed a basic test meal of rice and vegetable soup seasoned with isotopically labeled, iron fortified fish sauce. RESULTS: Iron absorption was significantly lower from ferrous lactate and from ferric ammonium citrate fortified fish sauce than from ferrous sulfate fortified fish sauce. Fractional iron absorption (geometric mean; -1s.d., +1s.d.) was 8.7(3.6; 21.4)% for ferrous lactate compared to 13.0(5.4; 31.4)% from ferrous sulfate, P = 0.003 (study 1) and 6.0(2.5; 14.3)% from ferric ammonium citrate relative to 11.7(4.4; 30.7)% from ferrous sulfate, P < 0.001, in study 2. Citric acid added at a molar ratio of approximately 2.5 to iron had no effect on iron absorption from ferrous sulfate (study 3). Iron absorption in the presence of citric acid was 14.1(6.4; 30.8)% compared to 12.0(5.8; 24.7)% in its absence (P = 0.26). CONCLUSIONS: Iron absorption was 50-100% higher from ferrous sulphate fortified fish sauce than from fish sauce fortified with ferric ammonium citrate or ferrous lactate. In the presence of citric acid as a chelator, ferrous sulfate would appear to be a useful fortificant for fish sauce. SPONSORSHIP: International Atomic Energy Agency (IAEA), Vienna, Austria.

The potential of inorganic mass spectrometry in mineral and trace element nutrition research.

Over the past two decades, new applications of inorganic mass spectrometry have been made possible by the use of stable isotopes as tracers in studies of mineral and trace element metabolism in man. Stable isotope techniques and radioisotope methods are the only reliable tools available for determination of the absorption, retention, or utilization of a nutrient by the human body. Recent developments in inorganic mass spectrometry might open new perspectives as progress in this field of research depends mainly on improving existing stable isotope techniques and on developing novel concepts. By improving precision in isotope analysis, isotope doses in experiments on man can be reduced to physiologically more meaningful levels. This will also enable reduction of the (often substantial) costs of isotopically labeling a nutrient in a test meal. Improvements in the mass spectrometric sensitivity will enable the development of new tracer techniques that have the potential to provide the information required by: 1. governmental institutions for designing food fortification programs; 2. the food industry for developing nutrient-fortified food products; and 3. public health authorities for establishing reliable dietary recommendations for intake of inorganic nutrients. In this context the current scope and limitations of thermal ionization mass spectrometry, inductively coupled mass spectrometry, accelerator mass spectrometry, and resonance ionization mass spectrometry are evaluated. Iron isotopic variations in the human body are discussed as a possible source of bias that might be a future biological limit to stable isotope-dose reduction in experiments on iron metabolism in man.

Improving iron absorption from a Peruvian school breakfast meal by adding ascorbic acid or Na2EDTA.

BACKGROUND: Iron-fortified school breakfasts have been introduced in Peru to combat childhood iron deficiency. OBJECTIVE: We evaluated whether iron absorption from a school breakfast meal was improved by increasing the ascorbic acid content or by adding an alternative enhancer of iron absorption, Na2EDTA. DESIGN: In a crossover design, iron absorption from test meals was evaluated by erythrocyte incorporation of 58Fe and 57Fe. The test meals (wheat bread and a drink containing cereal, milk, and soy) contained 14 mg added Fe (as ferrous sulfate) including 2.0-2.6 mg 58Fe or 4.0-7.0 mg 57Fe. RESULTS: Geometric mean iron absorption increased significantly from 5.1% to 8.2% after the molar ratio of ascorbic acid to fortification iron was increased from 0.6:1 to 1.6:1 (P < 0.01; n = 9). Geometric mean iron absorption increased significantly from 2.9% to 3.8%, from 2.2% to 3.5%, and from 2.4% to 3.7% after addition of Na2EDTA at molar ratios relative to fortification iron of 0.3:1, 0.7:1, and 1:1, respectively, compared with test meals containing no added enhancers (P < 0.01; n = 10 for all). Iron absorption after addition of ascorbic acid (molar ratio 0.6:1) was not significantly different from that after addition of Na2EDTA (molar ratio 0.7:1). CONCLUSIONS: Ascorbic acid and Na2EDTA did not differ significantly in their enhancing effects on iron absorption at molar ratios of 0.6:1 to 0.7:1 relative to fortification iron. Additional ascorbic acid (molar ratio 1.6:1) increased iron absorption significantly. Increasing the molar ratio of Na2EDTA to fortification iron from 0.3:1 to 1:1 had no effect on iron absorption.

Iron absorption from experimental infant formulas based on pea (Pisum sativum)-protein isolate: the effect of phytic acid and ascorbic acid.

Infant formula based on pea (Pisum sativum)-protein isolate has been suggested as an alternative to soybean formula in countries where soybean is not a native crop, or when soybean protein cannot be used due to allergic reactions or intolerances. In the present study, Fe absorption from experimental infant formulas based on pea-protein isolate was measured in healthy non-anaemic young women. The influence of phytic acid and ascorbic acid on Fe absorption was evaluated, using a stable-isotope technique based on incorporation of Fe stable-isotope labels into erythrocytes 14 d after administration. Geometric mean Fe absorption increased from 20.7 (+1 SD 41.6, -1 SD 10.3) % to 33.1 (+1 SD 58.6, -1 SD 18.7) %; (P < 0.0001; n 10) after enzymic degradation of virtually all phytic acid. Doubling the molar ratio Fe:ascorbic acid from 1:2.1 to 1:4.2 in the infant formula with native phytic acid content also increased Fe absorption significantly (P < 0.0001; n 10); geometric mean Fe absorption increased from 14.8 (+1 SD 32.1, -1 SD 6.8) % to 22.1 (+1 SD 47.2, -1 SD 10.4) %. These results confirm the inhibitory and enhancing effects of phytic acid and ascorbic acid respectively on Fe absorption, but also indicate relatively high fractional Fe absorption from the pea-protein-based formulas. After adjusting for differences in Fe status, our data indicate that Fe absorption from dephytinised pea protein might be less inhibitory than dephytinised soybean protein as measured in a previous study (Hurrell et al. 1998).

The influence of meat on nonheme iron absorption in infants.

During weaning the infant has a high iron requirement, and highly available dietary iron is needed to ensure optimal iron status. Muscle tissue has been identified as an enhancer of nonheme iron absorption in adults, although the influence of meat on nonheme iron absorption in infants has not been previously reported. The effect of the addition of 25 g of meat (lean beef) on nonheme iron absorption from a home-prepared vegetable purée meal (80 g of vegetables) was investigated in infants in the present study. The meals did not differ in their contents of other known enhancers or inhibitors of nonheme iron absorption. Incorporation of stable isotopes of iron (57Fe and 58Fe) into red blood cells 14 d after intake was used to measure iron absorption, using a cross-over design in eight healthy infants 43-49 wk of age. Nonheme iron absorption was significantly increased (p = 0.002) from the vegetable purée with added meat (geometric mean 15.0%) compared with the puréed vegetables (geometric mean 9.9%). These results thus suggest that meat is also an enhancer of nonheme iron absorption in infants and that nonheme iron absorption from weaning foods can be increased by the addition of meat.

Influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink in Jamaican children.

The influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink (6.3 mg total Fe per serving) was evaluated with a stable-isotope technique in 20 6-7-y-old Jamaican children. Each child received two test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2 consecutive days. Three different doses of ascorbic acid (0, 25, and 50 mg per 25-g serving) were evaluated in two separate studies by using a crossover design. Iron isotope ratios were measured by negative thermal ionization mass spectrometry. In the first study, iron absorption was significantly greater (P < 0.0001) after the addition of 25 mg ascorbic acid: geometric mean iron absorption was 1.6% (range: 0.9-4.2%) and 5.1% (2.2-17.3%) for the test meals containing 0 and 25 mg ascorbic acid, respectively. In the second study, a significant difference (P < 0.05) in iron absorption was observed when the ascorbic acid content was increased from 25 to 50 mg: geometric mean iron absorption was 5.4% (range: 2.7-10.8%) compared with 7.7% (range: 4.7-16.5%), respectively. The chocolate drink contained relatively high amounts of polyphenolic compounds, phytic acid, and calcium, all well-known inhibitors of iron absorption. The low iron absorption without added ascorbic acid shows that chocolate milk is a poor vehicle for iron fortification unless sufficient amounts of an iron-absorption enhancer are added. Regular consumption of iron-fortified chocolate milk drinks containing added ascorbic acid could have a positive effect on iron nutrition in population groups vulnerable to iron deficiency.

Influence of ascorbic acid on iron absorption from a iron-fortified, chocolate-flavored milk drink in Jamaican children

The influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink (6.3 mg total Fe per serving) was evaluated with a stable-isotope technique in 20 6-7-y-old Jamaican children. Each child received two test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2 consecutive days. Three different doses of ascorbic acid (0, 25, and 50 mg per 25-g serving) were evaluated in two separate studies by using a crossover design. Iron isotope ratios were measured by negative thermal ionization mass spectrometry. In the first study, iron absorption was significantly greater (P < 0.001) after the addition of 25 mg ascorbic acid; geometric mean iron absorption was 1.6 percent (range; 0.9-4.2 percent) and 5.1 percent (2.2-17.3 percent) for the test meals containing 0 and 25 mg ascorbic acid, respectively. In the second study, a significant difference (P < 0.05) in iron absorption was observed when the ascorbic acid content was increased from 25 to 50 mg: geometric mean iron absorption was 5.4 percent (range: 2.7-10.8 percent) compared with 7.7 percent (range: 4.7-16.5 percent), respectively. The chocolate drink contained low iron absorption without added ascorbic acid shows that chocolate milk is a poor vehicle for iron fortification unless sufficient amounts of an iron-absorption enhancer are added. Regular consumption of iron-fortified chocolate milk drinks containing added ascorbic acid could have a possible effect on iron nutrition in population groups vulnerable to iron deficiency(AU)