Lower Non-Heme Iron Absorption in Healthy Females from Single Meals with Texturized Fava Bean Protein Compared to Beef and Cod Protein Meals: Two Single-Blinded Randomized Trials.

Meat analogs based on plant protein extracts are rising in popularity as meat consumption declines. A dietary shift away from meat, which has a high iron bioavailability, may have a negative effect on the amount of iron absorbed from the diet. Iron absorption from legumes cultivated in regions not suitable for soy production, such as fava bean, has not yet been explored. The aim of this study was to evaluate non-heme iron absorption from a meal with texturized fava bean protein compared to beef and cod protein meals. The study included two single-blinded iron isotope trials in healthy Swedish women of the ages 18-45 years, each of whom served as their own control. The participants were served matched test meals containing beef and fava bean protein (Study 1) or cod and fava bean protein (Study 2) with radiolabeled non-heme iron 55Fe and 59Fe. The absorption of non-heme iron from test meals was measured by whole-body counting and erythrocyte incorporation. The absorption of non-heme iron, measured as erythrocyte incorporation ratio, from beef protein meal was 4.2 times higher compared to texturized fava bean meal, and absorption from cod protein meal was 2.7 times higher compared to the fava bean meal. The adjusted non-heme iron absorption, normalized to a 40% reference dose uptake, was 9.2% for cod protein meal, 21.7% for beef protein meal, and 4.2% for texturized fava bean meal. A fava bean protein meal has markedly lower iron bioavailability in healthy females compared with a meal of beef or cod protein. Therefore, a dietary shift from meat and fish protein to fava bean protein may increase the risk of iron deficiency.

Correction to: Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12 week, randomized, parallel-design intervention study.

ue to author error the paper was published wit.

Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention study.

PURPOSE: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. METHODS: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. RESULTS: Fifty-five females completed the study. There was a significant difference in change over time in total body iron stores between the two groups (p < 0.035). In the low-phytate bread group (n = 24) there were significant within-group decreases in both ferritin (mean 12%; from 32 ± 7 to 27 ± 6 µg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention CONCLUSIONS: In Swedish females of reproductive age, no statistically significant difference in iron status was detected after 12 weeks of high-phytate wholegrain bread consumption. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.

Is cord blood hepcidin influenced by the low-grade acute-phase response occurring during delivery? A small-scale longitudinal study.

AIM: To measure serum hepcidin in late pregnancy and in cord blood, and to analyze relationship between hepcidin, interleukin-6, and biomarkers of fetal iron status. MATERIALS AND METHODS: Data from 15 uncomplicated singleton pregnancies were analyzed longitudinally in trimester 3 (T3) and at birth. RESULTS: In T3, S-ferritin (median 14 µg/L) and transferrin (median 4.0 g/L) indicated low iron status, whereas the median soluble transferrin receptor (sTfR) was 4.0 mg/L, i.e. within the reference interval. Median T3 S-hepcidin was 7.8 ng/mL. Later on in cord blood, ferritin concentration (180 µg/L) were significantly higher, transferrin concentration (1.8 g/L) were significantly lower, and both sTfR (4.7 mg/L) and S-hepcidin concentrations (30.5 ng/mL) were significantly higher than maternal T3 concentrations. At the same time, cord blood interleukin-6 indicated an activated acute-phase reaction. In T3, after logarithmic transformation, there was a significant correlation between S-hepcidin and both S-ferritin (r = 0.691) and sTfR (r = -0.825). There was also a significant correlation between S-ferritin and both sTfR (r = -0.729) and transferrin (r = 0.549) in T3. CONCLUSIONS: Although S-ferritin, S-hepcidin, and sTfR were correlated during pregnancy, these relationships were not apparent in umbilical cord blood. Further, cord blood interleukin-6 indicated an activated acute-phase response, and sTfR, which is known to be unaffected by inflammation, indicated a low iron status in cord blood. Thus, instead of representing an enhanced iron status, the data appear to suggest that hepcidin and ferritin in cord blood may be influenced by the low-grade acute-phase response that occurs during delivery.

Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females-Double isotope sequential single-blind studies in menstruating women.

BACKGROUND: The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption. OBJECTIVE: The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843). STUDY DESIGN: With a single blinded placebo controlled sequential design, iron absorption from a light breakfast meal administered with or without capsules containing 1010 cfu freeze-dried Lp299v was studied in healthy female volunteers of fertile age. The methodology used was a double isotope technique (59Fe and 55Fe). Two studies were performed using the same protocol. RESULTS: In study 1, the absorption of iron from a meal without Lp299v was found to be 17.4 ± 13.4%, and from an identical meal with Lp299v was found to be 22.4 ± 17.3% (mean ± SD). This difference was statistically significant (p = 0.040, n = 14). In study 2, the absorption of iron from a meal without Lp299v was found to be 20.9 ± 13.1%, and from an identical meal with Lp299v found to be 24.5 ± 12.0% (mean ± SD, n = 28), which again was statistically significant (p = 0.003). CONCLUSION: Freeze-dried Lp299v enhances the absorption of iron when administered together with a meal with a high iron bioavailability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02131870.

Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age.

Iron deficiency is common, especially among young women. Adding probiotics to foods could be one way to increase iron absorption. The aim of this study was to test the hypothesis that non-haem iron absorption from a fruit drink is improved by adding Lactobacillus plantarum 299v (Lp299v). Iron absorption was studied in healthy women of reproductive age using a single-blind cross-over design in two trials applying the double-isotope (55Fe and 59Fe) technique. In Trial 1, iron absorption from a fruit drink containing 109 colony-forming units (CFU) Lp299v was compared with that from a control drink without Lp299v. Trial 2 had the same design but 1010 CFU were used. The test and control drinks contained approximately 5 mg of iron as ferrous lactate and were labelled with 59Fe (B) and 55Fe (A), respectively, and consumed on 4 consecutive days in the order AABB. Retention of the isotopes was measured with whole-body counting and in blood. Mean iron absorption from the drink containing 109 CFU Lp299v (28·6(sd 12·5) %) was significantly higher than from the control drink (18·5(sd 5·8) %), n 10, P<0·028). The fruit drink with 1010 CFU Lp299v gave a mean iron absorption of 29·1(sd 17·0) %, whereas the control drink gave an absorption of (20·1(sd 6·4) %) (n 11, P<0·080). The difference in iron absorption between the 109 CFU Lp299v and the 1010 CFU Lp299v drinks was not significant (P=0·941). In conclusion, intake of probiotics can increase iron absorption by approximately 50 % from a fruit drink having an already relatively high iron bioavailability.

Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist.

PURPOSE: To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS: Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS: The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION: The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.

Heme iron-based dietary intervention for improvement of iron status in young women.

OBJECTIVE: Conventional iron deficiency treatment with pharmacologic iron doses often causes side effects. Heme iron has high bioavailability and a low capacity to cause gastrointestinal side effects. This study investigated the possibility of using heme iron in the form of blood-based crisp bread as a diet-based treatment program to improve the iron status of women of reproductive age. METHODS: In a 12-wk intervention study, 77 women (mean age 24 y) were assigned to one of four groups: blood-based crisp bread (35 mg of iron [Fe], 27 mg of which was heme Fe), iron supplementation consisting of 35 mg of non-heme iron/day (Fe35), iron supplementation consisting of 60 mg of non-heme iron/day (Fe60), and controls (iron-free tablets). RESULTS: Body iron increased significantly in the crisp bread group by a median of 2.7 mg/kg (interquartile range 3.1, n = 18), in the Fe35 group by 2.7 mg/kg (interquartile range 2.8, n = 11), and in the Fe60 group by 4.1 mg/kg (interquartile range 3.6, n = 13), whereas no change was observed in the control group. No statistically significant difference in iron status increase was observed between the crisp bread group compared with the two iron-supplemented groups. CONCLUSION: Dietary-based treatment containing heme iron has few side effects and can be used efficiently to improve the iron status of women of reproductive age.

Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery.

Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.

Iron status in Swedish teenage girls: impact of low dietary iron bioavailability.

OBJECTIVE: Although it is well known that bioavailability of iron in the diet is important, it has not been fully elucidated in practice. We investigated iron intake and iron absorption in the ordinary diet of free-living individuals in relation to iron status and assessed iron requirements. METHODS: From a total of 1245 adolescent boys and girls included in the Göteborg Adolescence Study of food habits, 28 adolescent girls registered their food intake during 7 d. Iron intake was assessed on the basis of these 7-d dietary records. Iron absorption was calculated using an algorithm including enhancing and inhibiting dietary factors on iron absorption in relation to individual iron status. RESULTS: Available iron intake was 11.5 +/- 2.8 mg/d (mean +/- SD). The proportion of girls with an iron intake below the Nordic nutrition recommendations was 85% (n = 24). Calculated iron absorption was 1.09 +/- 0.59 mg/d (mean +/- SD). Only four girls satisfied their estimated individual iron requirement concerning the absorbed amount of iron. Iron depletion (serum ferritin concentration < or = 15 microg/L) was present in 10 girls (36%), 2 of whom were also anemic (hemoglobin concentration < or = 120 g/L). CONCLUSION: Swedish adolescent girls seemed to have difficulties satisfying their iron requirement in terms of absorbed amount. The data support the view that iron intake and bioavailability of dietary iron is important when evaluating whether iron requirements have been met.

The relative bioavailability in humans of elemental iron powders for use in food fortification.

BACKGROUND: Bioavailability data in humans of elemental iron powders is limited although elemental iron is a common form of iron when used as a fortificant. AIM OF THE STUDY: The relative bioavailability (RBV) of seven elemental iron powders, five commercially available and two developmental are evaluated. In addition, one commercial electrolytic iron powder given with ascorbic acid (AA) was examined. METHODS: Based on a validated method this double-blinded randomized crossover study included three groups of male blood donors (n = 3*16) who were served rolls fortified with different elemental iron powders or ferrous sulfate (FeSO(4)) nine weeks apart. Blood samples were drawn every hour for six hours. RBV was obtained by comparing the increase in serum iron concentration induced by the elemental iron with the increase induced by FeSO(4). RESULTS: All elemental iron powders studied were significantly less well absorbed compared to FeSO(4). The electrolytic iron given with 50-mg AA was as well absorbed as FeSO(4) (molar ratio = 1:6, AA:Fe). The mean RBVs of the iron powders were: electrolytic (A-131, RBV = 0.65); electrolytic (Electrolytic, RBV = 0.59); carbonyl (Ferronyl, RBV = 0.58); H-reduced (AC- 325, RBV = 0.56); H-reduced (Hi-Sol, RBV = 0.50); carbonyl (CF, RBV = 0.37); reduced (Atomet 95SP, RBV = 0.36). The reduced iron was distinguished by having significantly lower RBV (0.36) although no significant overall ranking was possible. CONCLUSION: Based on a validated method this doubleblinded cross-over study in humans showed that the evaluated elemental iron powders currently available for commercial use are significantly less well absorbed compared to FeSO(4). The results indicate that the reduced iron powder was absorbed to a lower extent compared to the other iron powders and only 36% compared to FeSO(4). Ascorbic acid seems to improve the bioavailability of elemental iron even though a rather low molar ratio is used. Thus, if confirmed, this enhancing effect of ascorbic acid on elemental iron when used as a fortificant could be used by co-fortifying them.

Validation of the clinical approach of using the induced serum iron increase after 1h as a measure of iron absorption.

BACKGROUND & AIMS: To evaluate the correlation between the iron absorption and the induced increase in serum iron concentration (S-Fe) after 1 h. METHODS: Eleven subjects were after an over night fast served a wheat roll fortified with 100-mg iron as ferrous sulfate labelled with radio iron. The S-Fe response and the iron absorption measured by whole body counting, were studied. RESULTS: There was a significant correlation between the iron absorption and the S-Fe increase (R2 = 0.75, P < 0.001). CONCLUSION: This short and valid observation period proposes the S-Fe procedure as an uncomplicated and clinically applicable tool when evaluating the iron absorption capacity of patients.

The validation of using serum iron increase to measure iron absorption in human subjects.

The objectives of the present study were to study the correlation between the change in serum Fe and Fe absorption when administering 100 mg Fe (as FeSO4) orally, and to study the correlation between the absorption from a 3 mg and a 100 mg Fe (as FeSO4) dose. The study was conducted in a group of eleven male blood donors, without any evident infection, who had given blood 8 weeks before the study. On three consecutive mornings the subjects were served a wheat roll fortified with Fe. On the first 2 d the roll was fortified with 3 mg Fe labelled with 59Fe; on day 3 the roll was fortified with 100 mg Fe labelled with 55Fe. The serum Fe response to the 100 mg dose was followed for 6 h. Fe absorption was measured by whole-body counting. High correlations were seen between the absorption of Fe and the change in serum Fe after 100 mg Fe (r2 0.94, P<0.001), between the absorption from 3 mg and 100 mg Fe (r2 0.88, P<0.001), and between the absorption from 3 mg Fe and change in serum Fe after 100 mg Fe (r2 0.90, P<0.001). This strengthens the evidence that it is possible to use the change in serum Fe as a measure of Fe absorption, e.g. when establishing the relative bioavailability for Fe powders. The results also imply that the induced serum Fe increase following 100 mg Fe added to a food could predict the Fe absorption of a small dose of Fe added to the same meal.

The role of meat to improve the critical iron balance during weaning.

BACKGROUND: Iron requirements during the weaning period are the highest per unit body weight during human life, and diet is often insufficient to cover iron needs. For the first time in infant nutrition the absorption of both nonheme and heme iron from a typical weaning gruel after addition of meat with and without ascorbic acid (AA) to improve bioavailability was studied. METHODS: Nonheme and heme iron absorption from gruel was measured in 33 adults using 2 radioiron isotopes--an inorganic iron salt to label nonheme iron, the other biosynthetically labeled rabbit hemoglobin to label heme iron. Iron absorption was measured from the basal gruel (based on milkpowder and cereals) and from basal gruel added 20 g red powdered meat, alone and together with 20 mg AA in 4 different trials. RESULTS: Nonheme iron absorption from the basal meal was 0.33 mg/1000 kcal and the increase from added 20 mg AA was 39%, whereas addition of red meat increased nonheme iron absorption by 85%. This latter increase was unexpectedly high. Total iron absorption was further increased by heme iron absorption of 0.23 mg Fe/1000 kcal. When adding both meat and AA, total iron absorption amounted to 1.08 mg iron/1000 kcal, ie, exceeding 1 mg/1000 kcal, a level estimated to correspond with daily iron requirements in 95% of infants aged 12 months. CONCLUSIONS: Addition of powdered red meat to weaning gruels markedly increased total iron absorption. A weaning diet with added powdered meat and AA may serve as a viable option to satisfy the body's high iron requirements during this critical period.