Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in nonanemic women

BACKGROUND: Recent studies in humans suggest that ferritin iron in soybeans has high bioavailability. However, direct evidence for this is lacking because the soybeans were intrinsically labeled; thus, iron bound to other ligands, such as phytate, was also labeled. OBJECTIVE: The objectives of the study were to evaluate the absorption of iron from extrinsically labeled, purified ferritin (horse spleen) reconstituted with either high-phosphate iron mineral (plant-type) or low-phosphate iron mineral (animal-type) and to compare it with iron absorption from ferrous sulfate. DESIGN: Nonanemic, healthy young women were fed a standard breakfast meal supplemented with (59)Fe-labeled ferritin or ferrous sulfate, in randomized order. Fifteen subjects received ferritin with the low-phosphate iron mineral, and 15 subjects received ferritin with the high-phosphate iron mineral. Iron absorption was measured in a whole-body counter after 14 and 28 d and by red blood cell incorporation after 28 d. RESULTS: There was no significant difference in iron absorption between ferritin and ferrous sulfate: low-phosphate iron mineral ferritin (x +/- SD: 21.4 +/- 14.7%) compared with ferrous sulfate (21.9 +/- 14.6%), or high-phosphate iron mineral ferritin (22.2 +/- 19.2%) compared with ferrous sulfate (16.7 +/- 7.1%). Results obtained by using whole-body retention of iron and red blood cell incorporation differed with the type of iron, which suggests that pathways for iron uptake and utilization differed for the 2 forms. CONCLUSIONS: Iron is equally well absorbed from ferritin and ferrous sulfate independent of the phosphate content of the ferritin iron mineral. Thus, dietary ferritin iron is likely to be a good source of iron.     

Absorption of iron from recombinant human lactoferrin in young US women

BACKGROUND: Lactoferrin is a major protein component of human milk, and it binds iron with high affinity. Because the human small intestine has receptors for lactoferrin, a role for it in iron absorption has been suggested. OBJECTIVE: The objective was to study the absorption of iron from extrinsically labeled purified recombinant human lactoferrin produced in rice and to compare it with the absorption of iron from ferrous sulfate. DESIGN: On 2 occasions 4 wk apart, healthy young women (n = 20) were fed a standardized meal supplemented in randomized order with 59Fe as lactoferrin or as ferrous sulfate. Ten subjects received lactoferrin that had been heat-treated, and 10 subjects received untreated lactoferrin. Iron absorption was measured in a whole-body counter after 14 and 28 d and also was measured by red blood cell incorporation after 28 d. RESULTS: The difference in whole-body iron absorption between heat-treated (24.6 +/- 20.8%; n = 10) and untreated (16.2 +/- 4.4%; n = 10) lactoferrin was not significant. The difference in whole-body iron absorption between the groups given lactoferrin (20.4 +/- 15.3%; n = 20) or ferrous sulfate (18.8 +/- 13.2%; n = 20) also was not significant. Serum ferritin and iron absorption were inversely correlated in subjects when they received either lactoferrin or ferrous sulfate, which suggested that iron is absorbed from the 2 sources by a similar mechanism. CONCLUSIONS: Iron is equally well absorbed from lactoferrin (whether heat-treated or untreated) and ferrous sulfate. Thus, iron provided by dietary lactoferrin is likely to be well utilized in human adults.     

Green tea or rosemary extract added to foods reduces nonheme-iron absorption

BACKGROUND: Phenolic compounds act as food antioxidants. One of the postulated mechanisms of action is chelation of prooxidant metals, such as iron. Although the antioxidative effect is desirable, this mechanism may impair the utilization of dietary iron. OBJECTIVE: We sought to determine the effect of phenolic-rich extracts obtained from green tea or rosemary on nonheme-iron absorption. DESIGN: Young women aged 19-39 y consumed test meals on 4 separate occasions. The meals were identical except for the absence (meal A) or presence (meal B) of a phenolic-rich extract from green tea (study 1; n = 10) or rosemary (study 2; n = 14). The extracts (0.1 mmol) were added to the meat component of the test meals. The meals were extrinsically labeled with either 55Fe or 59Fe and were consumed on 4 consecutive days in the order ABBA or BAAB. Iron absorption was determined by measuring whole-body retention of 59Fe and the ratio of 55Fe to 59Fe activity in blood samples. RESULTS: The presence of the phenolic-rich extracts resulted in decreased nonheme-iron absorption. Mean (+/-SD) iron absorption decreased from 12.1 +/- 4.5% to 8.9 +/- 5.2% (P < 0.01) in the presence of green tea extract and from 7.5 +/- 4.0% to 6.4 +/- 4.7% (P < 0.05) in the presence of rosemary extract. CONCLUSION: Phenolic-rich extracts used as antioxidants in foods reduce the utilization of dietary iron.     

Increasing the cooking temperature of meat does not affect nonheme iron absorption from a phytate-rich meal in women

The effect of increasing cooking temperatures of meat on nonheme iron absorption from a composite meal was investigated. Cysteine-containing peptides may have a role in the iron absorption enhancing effect of muscle proteins. Heat treatment can change the content of sulfhydryl groups produced from cysteine and thereby affect iron absorption. Twenty-one women (25 +/- 3 y) were served a basic meal without meat and two other meals consisting of the basic meal plus 75 g of pork meat cooked at 70, 95 or 120 degrees C. The meals were extrinsically labeled with (55)Fe or (59)Fe. Iron absorption was determined from measurements of whole-body (59)Fe retention and the activity of (55)Fe and (59)Fe in blood samples. Nonheme iron absorptions were 0.9 (0.5-4.0)% (P = 0.06), 0.7 (0.4-3.9)% (P = 0.1) and 2.0 (1.3-3.1)% (P < 0.001) greater when meat cooked at 70, 95 or 120 degrees C, respectively, was added to the basic meal. Increasing the cooking temperature of meat did not impair nonheme iron absorption compared with cooking at 70 degrees C. Because the cysteine content of meat decreased with increasing cooking temperature, this argues against a specific contribution of sulfhydryl groups from cysteine residues in the promotion of nonheme iron absorption by meat proteins.     

Fortification iron as ferrous sulfate plus ascorbic acid is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women

The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished with nonisotopically labeled serum iron curves. Using stable isotope appearance curves (SIAC) in serum, we measured iron absorption profiles from FeSO(4) with ascorbic acid (AA) and from NaFeEDTA, as well as the serum hepcidin and NTBI response following the meals. Healthy women (n = 16) were given 6 mg oral iron as labeled FeSO(4) and NaFeEDTA with a maize porridge using a crossover design. SIAC, NTBI, and serum hepcidin were measured over 8 h after the meal. Iron from FeSO(4) plus AA was more rapidly absorbed, resulting in a 35% greater relative AUC during the first 2 h than for NaFeEDTA (P < 0.001). Median (95% CI) fractional iron absorption from the FeSO(4)- and NaFeEDTA-fortified meals was 15.2% (11.0-19.5) and 6.0% (5.0-9.2), respectively (P < 0.001). In response to the FeSO(4)-fortified meal, there was an ~60% increase in median serum hepcidin (P < 0.05) but no significant change in NTBI. There was no significant change in serum hepcidin or NTBI after the NaFeEDTA-fortified meal. SIAC are a useful new tool to compare iron absorption profiles from different iron compounds in fortified foods. Even with the use of a very well absorbed ferrous iron compound, iron fortification in this population does not increase NTBI, suggesting a low risk for adverse health consequences.     

An irradiated electrolytic iron fortificant is poorly absorbed by humans and is less responsive than FeSO4 to the enhancing effect of ascorbic acid

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.     

Iron absorption by healthy women is not associated with either serum or urinary prohepcidin

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.     

Nonheme-iron absorption from a phytate-rich meal is increased by the addition of small amounts of pork meat

BACKGROUND: Muscle tissue from various sources is known to promote nonheme-iron absorption. However, systematic studies of the dose dependency of this effect of meat on iron absorption from an inhibitory meal with low amounts of meat are lacking. OBJECTIVE: We investigated the dose-response effect of small amounts of meat on nonheme-iron absorption from a meal presumed to have low iron bioavailability. DESIGN: Forty-five healthy women with a mean (+/-SD) age of 24 +/- 3 y were randomly assigned to 1 of 3 groups, each of which was served (A) a basic meal (rice, tomato sauce, pea purée, and a wheat roll) and (B) the basic meal with either 25, 50, or 75 g pork (longissimus muscle). Meal A contained 2.3 mg nonheme iron, 7.4 mg vitamin C, and 220 mg (358 micro mol) phytate. Each meal was served twice, and the order of the meals was ABBA or BAAB. The meals were extrinsically labeled with (55)Fe or (59)Fe. Iron absorption was determined from measurements of (59)Fe whole-body retention and the activity of (55)Fe and (59)Fe in blood samples. RESULTS: Twenty-five grams meat did not increase nonheme-iron absorption significantly (P = 0.13), whereas absorption increased 44% (P < 0.001) and 57% (P < 0.001), respectively, when 50 and 75 g meat were added to the basic meal. In absolute values, this corresponds to an absorption that was 2.6% and 3.4% higher, respectively, than that with the basic meal after adjustment of the data to a level of 40% absorption from a reference dose. CONCLUSION: Small amounts of meat (>or=50 g) significantly increase nonheme-iron absorption from a phytate-rich meal low in vitamin C.     

Iron absorption from ferrous bisglycinate and ferric trisglycinate in whole maize is regulated by iron status

BACKGROUND: There is a need to determine whether iron absorption from iron amino acid chelates is protected from inhibition by dietary phytate and regulated normally by iron status. OBJECTIVE: The objective of this study was to compare iron absorption from ferrous sulfate, ferrous bisglycinate, and ferric trisglycinate in whole-maize meal; to determine whether iron from ferrous bisglycinate and ferrous sulfate exchanges in the intestinal pool; and to assess iron absorption from ferrous bisglycinate and ferric trisglycinate over a range of iron statuses. DESIGN: In study 1A, 10 iron-sufficient men consumed ferrous sulfate-fortified whole-maize meal porridge equilibrated with (59)Fe-sulfate on day 1 and (55)Fe-bisglycinate on day 2. In study 1B, these volunteers consumed ferrous sulfate-fortified porridge equilibrated with (59)Fe-sulfate and (55)Fe-bisglycinate simultaneously. In studies 2A and 2B, iron absorption from 3 mg Fe as (59)Fe-ascorbate, (55)Fe-bisglycinate, or (59)Fe-trisglycinate in water and in porridge was compared in 23 subjects with a range of iron statuses. Iron absorption was determined from blood radioactivity on day 16. RESULTS: In study 1A, geometric mean iron absorption from ferrous bisglycinate was 6.0% (range: 2.6-13.6%), 4 times higher than that from ferrous sulfate (1. 7%; range: 1.0-3.3%; P < 0.05). In study 1B, absorption from neither source was different from that in study 1A. In studies 2A and 2B, absorption from all sources was strongly inversely related to serum ferritin, with geometric means of 32.5% (iron ascorbate), 9.1% (bisglycinate), and 15.3% (trisglycinate). Iron from ferric trisglycinate was poorly absorbed (2.3%; range: 0.5-9.2%) from maize. CONCLUSION: In whole-maize meal, iron from ferrous bisglycinate is better absorbed than is iron from ferrous sulfate and does not exchange with iron from maize or ferrous sulfate in the intestinal pool. Absorption of iron from bisglycinate and trisglycinate is regulated normally by iron status.     

The effect of three types of saponin on iron and zinc absorption from a single meal in the rat

1. Iron and zinc retentions in young male rats, given 3 g starch-sucrose paste containing 120 micrograms Fe as FeSO4 or 139 micrograms Zn as ZnCl2 (extrinsically labelled with 59Fe or 65Zn) and increasing amounts of Gypsophila saponins, were measured by whole-body counting. The results were compared with whole-body Fe and Zn retention from a meal containing crude or purified saponin fractions. In a separate experiment Fe retention from a meal containing Gypsophila saponins, soyasaponin I, or saponins extracted from lucerne (Medicago sativa) plant tops, was measured in older rats. 2. Results indicated that Fe absorption decreased with increasing concentration of Gypsophila saponins. This was significant at a saponin:Fe molar value of approximately 1, with maximum effect occurring at molar ratios of 4 and above, when Fe absorption was reduced by approximately 17%. Gypsophila saponins had no effect on Zn absorption from a test meal. 3. Fe absorption was similar in groups given purified or crude Gypsophila saponins at the same saponin:mineral molar value of 8, demonstrating that the 'non-saponin' fraction of the commercial preparation does not affect the absorption of this mineral. 4. Saponins extracted from lucerne plant tops, fed at a saponin:Fe value of approximately 8, also reduced Fe absorption from a single meal. Fe absorption from a meal containing a similar amount of soyasaponin I was not significantly different from controls. 5. These results indicate that some dietary saponins may reduce Fe absorption and hence have an adverse effect on Fe status in man and simple-stomached animals.     

Women with low iron stores absorb iron from soybeans

BACKGROUND: Worldwide, 30% of the population, a greater proportion of whom are women and children, is iron deficient. Soybeans are a major source of nonheme iron in many human diets, but information on iron bioavailability is still conflicting. Because much of soybean iron is in ferritin [distinct from the poorly bioavailable iron in cereals resulting from interactions between calcium, Fe(III), phytate, and proteins in the meal], soybeans provide a target for manipulating seed iron composition to achieve increased iron bioavailability. OBJECTIVE: The aim was to reevaluate soybean iron bioavailability. DESIGN: Eighteen women, most with marginal iron deficiency, consumed meals with intrinsically labeled ((55)Fe) soybeans (hydroponically grown and nonnodulating) as soup (n = 11) or muffins (n = 7) and a reference dose of (59)Fe as ferrous sulfate in ascorbate solution. The radioactivity in red cells was measured 14 and 28 d later. RESULTS: The mean (55)Fe absorption from either soup or muffins was 27% and that from the reference dose was 61%. (55)Fe was distributed approximately equally between protein (49.3 +/- 3.0%) and phytate, a contrast with nodulating soybeans likely caused by a high phosphate content in the growth medium. There was an expected inverse correlation (r = -0.793, P < 0.001) between red cell radioactivity and serum ferritin concentration. CONCLUSIONS: These results show that soybeans appear to be a good source of nutritional iron in marginally iron-deficient individuals. More study is needed on the effect of plant nodulation on the form of soybean iron, aimed at enhancing bioavailability to combat iron deficiency in at-risk populations.     

Na2EDTA enhances the absorption of iron and zinc from fortified rice flour in Sri Lankan children

Rice flour was proposed as a vehicle for iron and zinc fortification in Sri Lanka. Although widely consumed, rice flour has not been evaluated as a fortified food, and the absorption of minerals including iron and zinc from this flour is unknown. Determination of the bioavailability of these nutrients is a critical step before commencing a fortification program. We randomly divided 53 Sri Lankan schoolchildren ages 6-10 y into 4 groups that consumed a local dish prepared with 25 g of fortified rice flour labeled with one of the following: 1) (58)FeSO(4) 2) (58)FeSO(4) + Na(2)EDTA 3) (58)FeSO(4) + (67)ZnO or, 4) (58)FeSO(4) + Na(2)EDTA + (67)ZnO. The levels of iron and zinc were 60 mg/kg; the rice flour also contained folate at 2 mg/kg in each group. Na(2)EDTA was added at a Fe:Na(2)EDTA, 1:1 molar ratio. A total of 48 children completed the trial. Absorption of (58)Fe from a meal was significantly greater (P < 0.01) in the groups administered FeSO(4) + Na(2)EDTA (4.7 +/- 3.6%) than in those administered FeSO(4) without Na(2)EDTA (2.2 +/- 1.3%). Fractional absorption of zinc was 13.5 +/- 6.0% in the FeSO(4) + Na(2)EDTA group and 8.8 +/- 2.0% in the FeSO(4) group (P = 0.037). Although zinc absorption was low, our results demonstrated a benefit in using Na(2)EDTA to improve both iron and zinc absorption. We conclude that the fortification of rice flour is feasible, although additional strategies such as dephytinization or an increase in the level of iron and zinc fortification should be considered to obtain a higher proportion of the daily requirement of total absorbed iron and zinc.     

Iron absorption is more closely related to iron status than to daily iron intake in 12- to 48-mo-old children

Few studies have evaluated iron absorption in small children after the first year of life. Our objectives were to examine the relations among iron intake, iron absorption, and iron status in a group of healthy children. We studied 28 children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative of their usual daily mineral intake. A multi-tracer stable isotope study was performed to assess iron absorption both from a meal ((58)Fe) and from a reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes. Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and more so to reference dose iron absorption (r(2) = 0.653, P < 0.0001). Iron absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049) but was not correlated with iron intake (P = 0.20). However, zinc intake was not correlated with measures of iron status, including reference dose iron absorption and serum ferritin (r(2) < 0.1, P > 0.25). Total absorbed iron was similar to needs estimated by the Institute of Medicine. We conclude that iron absorption in young children is more closely related to iron status than to iron intake. Reference dose iron absorption may be superior to serum ferritin as a surrogate measure for iron status in this age group. Although zinc intake may affect iron absorption from a meal, it does not appear to have a detectable effect on overall iron status in otherwise well-nourished children.     

Proline-rich proteins moderate the inhibitory effect of tea on iron absorption in rats

Tea inhibits iron absorption in studies in which tea is given with radiolabeled iron to humans as a single dose. Our objective was to test the hypothesis that proline-rich proteins (PRPs) may act as a defense against this effect by forming complexes with tannins, thereby preventing them from inhibiting iron absorption. Two studies were conducted. In study 1, rats were given test solutions containing (59)FeCl(3) in water, tea, or tea + gelatin (T/G). In study 2, the rats were divided into 3 groups and assigned to one of 3 nutritionally complete diets: control, tea (5 g tea tannin/kg diet), or T/G (5 g tea tannin + 60 g gelatin/kg diet). Rats were fed the respective diets for 5 d and then given a single (59)Fe-labeled meal of the diet. Iron absorption was measured by whole-body retention of the (59)Fe over a 2-wk period. Iron absorption in study 1 was lower in the tea group (24 +/- 9.6%, P < 0.05) than in the T/G (42 +/- 19.4%) or water groups (50 +/- 7.5%). In study 2, iron absorption did not differ among the groups. Rats fed the tea diet had dramatic hypertrophy of the parotid salivary glands. Adding gelatin as a proxy for salivary PRPs to the tea eliminated the inhibitory effect of tea on iron absorption. The results suggest that PRPs, whether from salivary glands or diet, can protect against the inhibition of iron absorption by tea.     

Sodium iron NaFeEDTA as an iron fortification compound in Central America. Absorption studies.

Studies were performed in seven children and 98 adults to compare the proportion of iron absorbed when administered as ferric sulfate (Fe2(SO4)3), NaFeEDTA, hemoglobin (Hb), and ferrous ascorbate. Studies in children (mostly iron deficient) showed that when the compounds were given with a milk-rice-sugar formula totalling 5 mg Fe, iron from hemoglobin was absorbed best, followed by NaFeEDTA and by Fe2(SO4)3 (mean percent absorption +/-SD = 34.5 +/- 1.5, 8.6 +/- 1.9 and 3.3 +/- 1.5, respectively). Studies in normal or iron deficient adults also demonstrated a better absorption of iron from NaFeEDTA than from Fe2(SO4)3 whether these compounds were given in an aqueous solution (5 mg Fe) or with a standard meal consisting of beans, tortillas, bread, and coffee providing also a total of 5 mg Fe. Hb iron under the same conditions was absorbed in the same proportion to the reference iron ascorbate, always being higher than iron absorbed from the other compounds. Fe2(SO4)3 and NaFeEDTA mixed in the same meal were absorbed in the same proportion as when NaFeEDTA alone was added to the meal and 2 to 3 times better than when Fe2(SO4)3 alone was added to the meal. Addition of desferrioxamine depressed iron absorption from Fe2(SO4)3 and NaFeEDTA, the latter being less affected. Addition of ascorbic acid increased absorption from both. When the compounds were added to the meal to provide 50 mg of iron, percent absorption was depressed in relation to the smaller iron dose in the case of Fe2(SO4)3 and Hb but remained unaltered in the case of NaFeEDTA. Addition of 45 mg Fe as Fe2(SO4)3 or NaFeEDTA to 0.4 mg Fe from the Hb in the meal did not change Hb iron absorption. Addition of 45 mg Fe as Hb or NaFeEDTA to 0.4 mg Fe from Fe2(SO4)3 in the meal enhanced iron absorption from the latter in the same proportions. Addition of 45 mg Fe as Fe2(SO4)3 and Hb to 0.4 mg Fe as NaFeEDTA in the meal respectively depressed and enhanced iron absorption from NaFeEDTA. These studies indicate that NaFeEDTA, Fe2(SO4)3 and nonheme food iron from a common pool different from the heme pool but which is changed in its characteristics by the presence of NaFeEDTA, resulting in a better absorption of iron.     

Riboflavin deficiency in the rat: effects on iron utilization and loss

Iron absorption and daily loss of Fe were measured in riboflavin-deficient (B2-) Norwegian hooded rats and controls (B2+). Animals were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. Riboflavin deficiency led to a reduction in the percentage of the 59Fe dose absorbed and an increased rate of 59Fe loss. All post-absorption 59Fe loss could be accounted for by faecal 59Fe, confirming that the loss was gastrointestinal. Fe concentrations and 59Fe as a percentage of retained whole-body 59Fe were higher in the small intestine of riboflavin-deficient animals than their controls, 14 d after the test meal. A separate experiment demonstrated that riboflavin deficiency was associated with a significant proliferative response of the duodenal crypts of the small intestine. These observations may explain the enhanced Fe loss in riboflavin deficiency.     

Iron absorption by humans from hemosiderin and ferritin, further studies.

Iron absorption from hemosiderin and ferritin biosynthetically labeled with radioactive iron has been studied in 61 subjects. The geometrical mean iron absorption from hemosiderin in both normal and iron deficient subjects was 3.4%. Its mean absorption ranged from 1.9% in normal subjects to 4.7% in subjects with moderate iron deficiency and 7.3% in subjects with marked iron deficiency. The iron absorption from hemosiderin was markedly increased when it was administered with ascorbic acid or liver. The absorption of iron from hemosiderin when hemosiderin and wheat were consumed in a meal, was lower than the absorption from wheat. Iron from liver ferritin and liver hemosiderin were less absorbed in this study than that previously reported for liver hemoglobin. The studies presented here support the possibility that ferritin and hemosiderin form an iron pool different from the non-heme pool formed by vegetal iron, egg iron and ferric and ferrous salts.     

The effect of riboflavin deficiency in rats on the absorption and distribution of iron

1. Riboflavin may play a part in the transport of iron across the gastrointestinal mucosa. Fe absorption was measured in the rat by monitoring whole-body retention of a dose of 59Fe using a small-animal gamma-counter. 2. Female Norwegian Hooded rats were fed on a diet deficient in riboflavin (B2-) from 5 weeks of age. Control animals, fed on a complete diet (B2+), were weight-matched to rats fed on the B2- diet. After 7 weeks all rats were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. 3. Riboflavin deficiency was associated with a reduction in the percentage of the dose absorbed and an increase in the rate of loss of Fe post absorption. 4. A smaller percentage of the absorbed dose was present in the livers of the riboflavin-deficient animals.     

Electrolytic iron or ferrous sulfate increase body iron in women with moderate to low iron stores

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.     

Factors affecting the absorption of iron from Fe(III)EDTA

1. The modification of iron absorption from Fe(III)EDTA by agents known to promote or inhibit absorption was examined in 101 volunteer multiparous Indian women. Fe absorption from Fe(III)EDTA was compared with absorption of intrinsic food Fe in a further twenty-eight subjects. Finally the urinary excretion of radio-Fe after oral administration of 59Fe(III)EDTA was studied in twenty-four subjects and evidence of intraluminal exchange of Fe was examined. 2. Fe absorption from maize porridge fortified with Fe(III)EDTA was more than twice that from porridge fortified with FeSO4 . 7H2O. 3. Although bran decreased Fe absorption from FeSO4 . 7H2O approximately 11-fold, it had no significant effect on Fe absorption from Fe(III)EDTA. Nevertheless tea, which is a more potent inhibitor of Fe absorption, decreased absorption from Fe(III)EDTA 7-fold. 4. Fe absorption from Fe(III)EDTA given in water was only increased 40% by addition of 3 mol ascorbic acid/mol Fe but by 7-fold when the relative proportions were increased to 6:1. This enhancing effect was blunted when the Fe(III)EDTA was given with maize porridge. In these circumstances, an ascorbate:iron value of 3:1 (which doubles absorption from FeSO4 . 7H2O) produced no significant increase in Fe absorption, while a value of 6:1 produced only a 2 . 5-fold increase. 5. Fe absorption from Fe(III)EDTA was not altered by addition of maize porridge unless ascorbic acid was present. 6. Less than 1% of 59Fe administered as 59Fe(III)EDTA was excreted in the urine and there was no inverse relationship between Fe absorption and the amounts excreted (r 0 . 58, P less than 0 . 05). 7. Isotope exchange between 59Fe(III)EDTA and 59FeSO4 . 7H2O was demonstrated by finding a similar relative value for the two isotopes in urine and erythrocytes when the two labelled compounds were given together orally. This finding was confirmed by in vitro studies, which showed enhanced 59Fe solubilization from 59FeSO4 . 7H2O in maize porridge when unlabelled Fe(III)EDTA was added. 8. Although Fe absorption from Fe(III)EDTA was marginally higher it appeared to form a common pool with intrinsic food iron in most studies. It is postulated that the mechanism whereby Fe(III)EDTA forms a common pool with intrinsic food Fe differs from that occurring with simple Fe salts. When Fe is present in the chelated form it remains in solution and is relatively well absorbed because it is protected from inhibitory ligands. Simple Fe salts, however, are not similarly protected and are absorbed as poorly as the intrinsic food Fe. 9. It is concluded that Fe(III)EDTA may be a useful compound for food fortification of cereals because the Fe is well absorbed and utilized for haemoglobin synthesis. The substances in cereals which inhibit absorption of simple Fe salts do not appear to inhibit absorption of Fe from Fe(III)EDTA.