Non-heme Iron Bioavailability Research Articles

Planetary Health Diet Compared to Dutch Dietary Guidelines: Nutritional Content and Adequacy.

In 2019, the EAT-Lancet Commission proposed a Planetary Health Diet (PHD) to address challenges toward sustainable and healthy diets. However, its suitability within the Dutch context and a comparison with the Dutch Dietary Guidelines (DDG) needs investigation. Our study aimed to compare the PHD with DDG in terms of food groups, servings, nutritional content, and adequacy in adults. We modeled two theoretical diets, the PHD (PHD-NL) and another based on the DDG (DDG-NL), using the Dutch National Food Consumption Survey (FCS-2016) and Dutch Food Composition Database to calculate the nutritional content and compared it with the Dutch Dietary Reference Values (DRVs). The PHD included higher quantities of vegetables, fish, legumes, and nuts, while the DDG suggested more significant amounts of cereals, tubers, starchy vegetables, dairy, and red meat. We observed differences in macronutrient distribution; while both diets lacked sufficient vitamin D, calcium content was lower in the PHD-NL. The PHD-NL had higher levels of fiber, vegetable protein, unsaturated fats, and non-heme iron, while vitamins B2, B6, B12, and calcium were lower than the DDG-NL diet. The PHD-NL has nutritional adequacy in the Dutch context, except for vitamin D and calcium, although it is essential to be cautious with iron because of the bioavailability of non-heme iron in plant-based diets. These findings have implications for the adoption of a sustainable diet according to nutritional requirements, population health status, and sociocultural context, as well as compliance with specific dietary behaviors of populations.

Pectin with Low Molecular Weight and High Degree of Esterification Increases Absorption of 58Fe in Growing Rats

Effects of pectins with different degrees of esterification (DE) and molecular weights (MW) on iron bioavailability were investigated in healthy growing rats by following erythrocyte incorporation of a dose of 58Fe. Rats were fed a control diet for 8 d and then deprived of food for 16 h. Two hours after the start of feeding iron-deficient diets, with or without pectin (80 g/kg diet), a dose of FeSO4 rich in 58Fe (60.28%) was intubated into the stomach; rats were then allowed to feed for an additional 4 h before withdrawal of food for 10 h. Rats were then fed iron-adequate diets for 9 d. The pectins differed in DE and MW, respectively, as follows: P-A (73%, 860,000), P-B (75%, 89,000), P-C (22%, 1,260,000) and P-D (24%, 114,000). Rats fed pectin-free diet with free access to food or restricted to the same quantity consumed by a respective pectin group served as controls. Iron absorption was 48% in the control group and 57% in rats fed P-B. Rats fed P-B had higher (P ≤ 0.05) serum iron, transferrin saturation, hematocrit and liver and spleen iron than the control group or the group fed P-C. These indices, except for transferrin saturation, were also higher in rats fed P-A and P-D compared with those fed P-C and controls, but to a lesser extent than in rats fed P-B. The data indicate that bioavailability of dietary non-heme iron was enhanced when pectin of low MW and high DE was added to the diet. This improvement was not evident with pectins having high MW and/or low DE.

Chemical depolymerisation of chondroitin sulfate glycosaminoglycan improves both antioxidant capacity and Fe uptake in a human intestinal Caco-2 cell model

Chondroitin sulfate (CS) is a high molecular weight sulfated polysaccharide that has been reported to improve joint health. A recent study has demonstrated the ability of enzymatically produced CS-oligosaccharides to improve non-heme iron bioavailability. In this research, CS was chemically hydrolyzed under acid, alkaline, and combined (acid & alkaline) conditions at 60 °C for different times (0–60 h) to understand if the oligosaccharides obtained can improve iron uptake in human intestinal Caco-2 cell model. The acidic hydrolyses produced a collection of desulfated and low molecular weight CS crude oligosaccharides (CS crude oligos), while under alkaline condition a high degree of deacetylation was detected with limited depolymerisation and desulfation. The combined treated CS was first degraded and desulfated in acid solution followed by alkali deacetylation. CS crude oligos produced by the combined treatment possessed the superior antioxidant capacity measured by ferric reducing and DPPH scavenging activities. All chemically hydrolyzed CS samples showed greater (p < 0.05) ferritin formation in Caco-2 cells compared to the negative control, where the greatest ferritin level was achieved by the combined treated CS. The depolymerisation of CS followed by the deacetylation created CS structural changes resulting in the increase of antioxidant and Fe-absorption enhancing capacities.

Effectiveness of Dietary Intervention with Iron and Vitamin C Administered Separately in Improving Iron Status in Young Women.

In order to maintain an adequate iron status in young women, effective dietary interventions should provide sufficient amounts of iron in everyday meals and improve the bioavailability of non-heme iron by providing vitamin C. While some intervention studies administering products rich in vitamin C in conjunction with iron sources showed improved iron status, it is unknown whether a separate administration of products rich in iron and vitamin C may be a successful strategy as well. The aim of this study was to assess the effectiveness of dietary intervention with iron and vitamin C administered separately in improving iron status in young women to prevent iron deficiency anemia. The study was conducted in a group of 29 women aged 18–30, and an 8-week dietary intervention was performed. Study participants with an adequate iron status received 50 g of iron-fortified oat flakes (as a source of non-heme iron) with breakfast and 200 mL of orange juice (as a source of vitamin C) in the second part of the day. Iron status was analyzed based on red blood cells, hemoglobin, hematocrit, serum ferritin, and serum iron, and it was assessed at baseline, after 4 weeks, and after 8 weeks of the intervention. The intakes of iron, vitamin C, and folate were controlled throughout the study period, and menstrual blood loss was estimated. After 8 weeks of intervention, statistically significant differences compared with baseline were observed only for hematocrit, as its level after 8 weeks of intervention was higher than the baseline (p = 0.0491). Comparing subsamples within the dietary intervention considered effective and ineffective for red blood cell levels, it was indicated that lower baseline vitamin C intake may result in a more effective dietary intervention (p = 0.0231). Comparing subsamples within the dietary intervention considered effective and ineffective for hemoglobin, hematocrit, iron, and serum ferritin levels, it was indicated that higher baseline levels of hemoglobin (p = 0.0143), hematocrit (p = 0.0497), iron (p = 0.0101), and serum ferritin (p = 0.0343) respectively may result in a more effective dietary intervention. It was concluded that dietary intervention with iron and vitamin C administered separately may be effective in improving iron status in young women to prevent iron deficiency anemia. It may be concluded that in the studied group, a better baseline iron status and lower baseline vitamin C intake may result in a more effective dietary intervention with iron and vitamin C administered separately to improve iron status in young women.

A sulfated polysaccharide from abalone influences iron uptake by the contrary impacts of its chelating and reducing activities

Polysaccharides with different structures have been reported to regulate iron uptake in opposite direction. The present study investigated the interaction between a sulfated polysaccharide (AGSP) from marine shellfishes and Fe(III)/Fe(II) in order to reveal the mechanism for the effect of AGSP on iron bioavailability. The Fe(III) chelating activity and resulting Fe(III)-chelates of AGSP and its desulfated derivative (dS-AGSP) were studied, their ferric reducing activity and Fe(II) chelating activity were compared, and their inhibition effects on the Fe absorption were evaluated by using Caco-2 cell models treated with Fe(III) and Fe(II). As indicated by the results, polysaccharides could chelate Fe(III) with the sulfate and carboxyl groups via FeO bond along with conformation change, resulting in unstable particles. Both AGSP and dS-AGSP inhibited the iron uptake in a dose-dependent manner. Notably, the chelating property of polysaccharides showed a negative correlation with the iron bioavailability while their reducing capability demonstrated a positive correlation. Moreover, sulfate substitution enhanced the chelating and reducing capabilities so to regulate the effects of AGSP on Fe absorption in contradictory ways. Thus, the present study elucidated the mechanism of the influence of AGSP on bioavailability of non-heme iron.

Salivary Cystatin SN Binds to Phytic Acid In Vitro and Is a Predictor of Nonheme Iron Bioavailability with Phytic Acid Supplementation in a Proof of Concept Pilot Study

ABSTRACTBackgroundAcute phytic acid intake has been found to decrease iron bioavailability; however, repeated phytic acid consumption leads to iron absorption adaptation. Salivary proline-rich proteins (PRPs) have been shown to inhibit iron chelation to tannins and may mediate similar iron absorption adaptation with phytic acid intake.ObjectivesThe objectives of this study were to determine whether salivary proteins bind to phytic acid in vitro, and to explore a proof of concept in a pilot study that examined the impact of 4-wk, daily phytic acid supplementation on individuals’ iron status, bioavailability, and salivary PRP concentrations.MethodsHigh-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization–time of flight were used to characterize in vitro salivary protein–phytic acid interactions. Nonanemic women (n = 7) consumed 350 mg phytic acid supplements 3 times daily for 4 wk, and meal challenges were employed to determine iron bioavailability, iron status, and salivary protein concentrations before and after supplementation periods. Enzyme-linked immunosorbent assay (ELISA) analysis of purified protein fractions and participant saliva identified proteins bound to phytic acid.ResultsIn vitro salivary protein–phytic acid interaction identified cystatin SN, a non–proline rich salivary protein, as the specific bound protein to phytic acid. Iron bioavailability (P = 0.32), hemoglobin (P = 0.72), and serum ferritin (P = 0.08) concentrations were not reduced from week 0 to week 4 after phytic acid supplementation. Basic PRPs and cystatin SN concentrations were positively correlated with iron bioavailability at week 4.ConclusionsOverall, results suggest that phytic acid binds to the non-PRP cystatin SN and that salivary protein production may improve iron bioavailability with phytic acid consumption.

Bioavailability and incorporation of nonheme iron from staple Chinese diet in young urban Chinese women

Background and Objectives: This study assessed the bioavailability and biological incorporation of nonheme iron from staple food diets in healthy young urban Chinese women and determined the relevant effects of typical regional patterns of staple foods in South and North China. Methods and Study Design: Twenty-two young urban Chinese women aged 20-23 years were enrolled and randomly allocated to two groups, with rice (rice group) and steamed buns (steamed buns group) as the staple food, respectively. Each participant received three meals daily containing approximately 3.25 mg of stable ^(57)FeSO_4 for 2 consecutive days, along with daily intravenous injection of approximately 2.0 mg of ^(58)FeSO_4. Nonheme iron absorption and infused iron incorporation rates were assayed. Results: In all participants, the rice group, and the buns group, nonheme iron intake was 7.2±1.6, 5.9±0.6, and 8.4±1.2 mg, respectively; mean ^(57)FeSO_4 absorption rate was 22.2%±9.6%, 22.2%±10.6%, and 22.2%±8.9%, respectively; and the mean infused ^(58)FeSO_4 incorporation rate was 91.6%±8.2%, 93%±7.3%, and 90%±9.1%, respectively. No substantial differences existed in the nonheme iron intakes and the ^(57)FeSO_4 absorption and ^(58)FeSO_4 incorporation rates between the rice and buns groups (all p＞0.05). Conclusions: The bioavailability and incorporation rates of nonheme iron from representative comprehensive Chinese diets in healthy young urban Chinese women were evaluated. Our results can facilitate the establishment of dietary reference intake for iron in Chinese women.

Bioavailability and incorporation of nonheme iron from a representative Chinese diet in young urban Chinese women.

This study assessed the bioavailability and biological incorporation of nonheme iron from staple food diets in healthy young urban Chinese women and determined the relevant effects of typical regional patterns of staple foods in South and North China. Twenty-two young urban Chinese women aged 20-23 years were enrolled and randomly allocated to two groups, with rice (rice group) and steamed buns (steamed buns group) as the staple food, respectively. Each participant received three meals daily containing approximately 3.25 mg of stable 57FeSO4 for 2 consecutive days, along with daily intravenous injection of approximately 2.0 mg of 58FeSO4. Nonheme iron absorption and infused iron incorporation rates were assayed. In all participants, the rice group, and the buns group, nonheme iron intake was 7.2±1.6, 5.9±0.6, and 8.4±1.2 mg, respectively; mean 57FeSO4 absorption rate was 22.2%±9.6%, 22.2%±10.6%, and 22.2%±8.9%, respectively; and the mean infused 58FeSO4 incorporation rate was 91.6%±8.2%, 93%±7.3%, and 90%±9.1%, respectively. No substantial differences existed in the nonheme iron intakes and the 57FeSO4 absorption and 58FeSO4 incorporation rates between the rice and buns groups (all p>0.05). The bioavailability and incorporation rates of nonheme iron from representative comprehensive Chinese diets in healthy young urban Chinese women were evaluated. Our results can facilitate the establishment of dietary reference intake for iron in Chinese women.

Effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age

IntroductionMicronutrient deficiencies are one of the most important public health issues worldwide and iron (Fe) deficiency anemia is the most prevalent micronutrient deficiency. Iron deficiency often coexists with calcium deficiency and iron and calcium supplementation often overlap. This has led to investigations into the interaction between these two minerals, and whether calcium may inhibit iron absorption in the gut. ObjectiveTo determine the effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age. MethodsA randomized and single blinded trial was conducted on 27 women of childbearing age (35–45 years old) divided into 2 groups (n1 = 13 and n2 = 14, respectively). On four different days, after an overnight fast, they received 5 mg of Fe as FeSO4 (labeled with 55Fe or 59Fe) with 800 mg of elemental calcium in the form of either calcium chloride, calcium gluconate, calcium citrate, calcium carbonate, calcium lactate, calcium sulfate or calcium phosphate. Calcium chloride was used as the control salt in both groups. Iron was labeled with the radioisotopes 59Fe or 55Fe, and the absorption of iron was measured by erythrocyte incorporation of radioactive Fe Results800 mg of elemental calcium as calcium citrate produced a significant decrease in non-heme iron bioavailability (repeated measures ANOVA, F = 3.79, p = 0.018). ConclusionOf the various calcium salts tested, calcium citrate was the only salt that decreased non-heme iron bioavailability relative to the calcium chloride control when taken on an empty stomach. These results suggest that inhibition of non-heme iron absorption in fasted individuals is dependent upon the calcium salt in question and not solely dependent on the presence of calcium.

Ascorbic Acid can Reverse the Inhibition of Phytic Acid, Sodium Oxalate and Sodium Silicate on Iron Absorption in Caco-2 cells.

The objective of the present study is to determine the effect of phytic acid (PA), sodium oxalate (SO) and sodium silicate (SS) on non-heme iron bioavailability in both the presence and absence of ascorbic acid (AA) using an in vitro digestion/Caco-2 cell model, and the levels of AA needed to promote Fe absorption from Fe complexed with PA, SO or SS were also determined. The results indicated that adding PA at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 55.80 %(P < 0.05), 72.33 % (P < 0.05), 73.32 % (P < 0.05), and 73.26 % (P < 0.05), respectively. Adding SS at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe also decreased ferrous iron uptake by 51.40 % (P < 0.05), 66.12 %(P < 0.05), 60.19 % (P < 0.05) and 45.11 % (P < 0.05), respectively. Adding SO at 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 40.81 % (P < 0.05) and 33.14 % (P < 0.05), respectively. When adding AA to iron plus organic acid medias reached molar ratios of 5:5:1 AA:PA:Fe, 3:5:1 AA:SO:Fe and 5:5:1 AA:SS:Fe, iron absorption from FeSO4 were significantly increased (P < 0.05). However, no significant effect was observed in iron absorption from FeCl3 when adding AA to the media. The results showed that PA, SS or SO decreases iron uptake from ferrous Fe, and AA can counteract their inhibiting effect on ferrous iron absorption and thus increase ferrous iron uptake. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.

Pectin Esterification Degree in the Bioavailability of Non-heme Iron in Women.

Pectins are a type of soluble fiber present in natural and processed foods. Evidence regarding the effect of esterification degree of pectins on iron absorption in humans is scarce. In the present study, the effect of pectins with different degrees of esterification on non-heme iron absorption in women was evaluated. A controlled experimental study was conducted with block design, involving 13 apparently healthy, adult women. Each subject received 5mg Fe (FeSO4) without pectin (control) or accompanied by 5g citrus pectin, two with a low degree of esterification (27 and 36%), and one with a high degree of esterification (67 to 73%), each on different days. Each day, the 5mg Fe doses were marked with radioactive 59Fe or 55Fe. Radioactivity incorporated into erythrocytes was determined in blood samples 14days after the marked Fe doses were consumed. On days 18 and 36 of study, 30 and 20mL blood samples were obtained, respectively, and blood sample radioactivity incorporated into erythrocytes was determined. Body iron status was determined from blood taken on day 18. Whole body blood volume was estimated for calculate iron bioavailability; it was assumed that 80% of absorbed radioactivity was incorporated into the Hb. All women participants signed an informed consent of participation at baseline. Iron bioavailability (mean geometric ±1 SD) alone (control) was 18.2% (12.3-27.1%), iron + pectin27 was 17.2% (10.2-29.2%), iron + pectin36 was 15.3% (9.5-24.6%), and iron + pectin67 was 19.5% (10.0-38.0%). No statistically significant differences between iron bioavailability (repeated measures ANOVA, p=0.22) were observed. Pectin esterification degree does not influence the bioavailability of non-heme iron in women.

Effects of different proteases on iron absorption property of egg white hydrolysates

One of the causes of iron deficiency in human is poor absorption of non-heme iron from the diet. While proteins from meats have been reported in the literature to enhance the absorption of non-heme iron, other proteins, such as those from egg, are known to inhibit iron absorption. The objective of this study is to investigate non-heme iron binding property of egg white proteins hydrolyzed using pepsin and a combination of bacterial/fungal proteases. The iron bioavailability of non-heme iron, in the presence of egg white (EW) hydrolysates, was evaluated in vitro using a tissues culture model system - rat intestinal epithelial cells (IEC-6). In the first treatment condition, EW was digested in the presence of ferrous gluconate (FeGluc), producing a peptide-FeGluc complex. In the second treatment, EW was digested in the absence of FeGluc followed by the addition of the non-heme iron. In both treatments, the resulting EW hydrolysates were further separated into >0.1–0.5kDa and >6–8kDa peptide fractions using dialysis. The hydrolysate and FeGluc complex or mixtures were applied to the IEC-6 cells and iron absorption was measured after 2h or 16h. Results showed that the peptide-FeGluc complex digested with a combined proteases from Bacillus licheniformis (SDAY) and from Aspergillus melluss (PP) increased the in vitro iron-binding property but did not enhance iron uptake by the in IEC-6 cells (p<0.05). Peptide-FeGluc complex digested with pepsin alone (>0.1–0.5kDa) resulted in significantly higher iron uptake in IEC-6 cells compared with the higher molecular weight complex (>6–8kDa) produced using the same hydrolysis treatment. Similarly, enhanced iron uptake was observed with the complexes produced with the combined SDAY and PP enzymatic treatments (>0.1–0.5kDa and >6–8kDa) (p<0.05). On the other hand, the enhanced iron absorption effect was not observed when pre-hydrolyzed free peptides were added to FeGluc. Overall, this study suggests that low molecular weight fractions of egg white protein hydrolysates can enhance the bioavailability of non-heme iron. Furthermore, the method by which the egg white proteins are being prepared, i.e., in the presence or absence of FeGluc, can affect the bioavailability of the non-heme iron.

Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55Fe and 59Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

Total Iron Bioavailability from the US Diet Is Lower Than the Current Estimate ,

Background: Total (heme and nonheme) iron bioavailability from the US diet has been estimated to be 18% based on a single human absorption study. New data, however, suggest that it may be time to revisit this estimate.Objective: We estimated total iron bioavailability from the US diet with the use of our recently reported algorithm that estimates nonheme iron absorption and a conservative value for heme iron absorption.Methods: We used dietary intake and biomarker information from the NHANES 2001–2002, MyPyramid Equivalents Database, and Food and Nutrient Database for Dietary Studies. The survey package in R software was used to estimate means and CIs, taking into account the strata, primary sampling units, and appropriate survey weight. We implemented 2 different approaches to estimate total iron absorption. In the first approach, we included all survey participants but adjusted the geometric mean of nonheme iron absorption to 15 μg ferritin/L serum to mimic values of individuals with no iron stores; in the second approach, absorption was estimated for only nonanemic subjects with no iron stores. A total sample size of 6631 was used based on availability of dietary and iron status biomarker data and C-reactive protein concentration ≤6 mg/L.Results: The geometric mean (95% CI) of unadjusted nonheme iron absorption for all subjects was 3.7% (3.6%, 3.8%), higher in female subjects [5.6% (5.4%, 5.7%)] than male subjects [2.6% (2.5%, 2.7%)] (P < 0.0001). Nonheme iron absorption was lower in non-Hispanic whites [3.5% (3.4%, 3.6%)] than Mexican Americans [4.5% (4.2%, 4.8%)] and non-Hispanic blacks [4.4% (4.1%, 4.7%)]. Estimated total iron absorption was 15.5% or 15.1%, depending on which approach was used to carry out the calculations.Conclusion: This study provides useful data for evaluating the current value of iron bioavailability from the US diet.

Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium

ObjectiveTo determine the effect of phytic acid, tannic acid and pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium. Research methodsTwenty-eight apparently healthy adult females participated in two iron absorption studies using radioactive iron isotopes (59Fe and 55Fe). One group received 5mg of iron (as FeSO4) alone (control), together with 10mg of phytic acid, 100mg of tannic acid and 250mg of pectin (study A), on different days. The second group received the same iron doses and compounds as the other group, plus 800mg of calcium (CaCl2) (study B). The compounds were administered after an overnight fast, and no food or beverages were consumed for the following 3h. Iron status and circulating radioactivity were measured in venous blood samples. ResultsThe geometric means of iron bioavailability (range±1SD) for iron alone, iron with phytic acid, iron with tannic acid, and iron with citrus pectin were 25.0% (11.9–52.0); 18.9% (9.9–35.8); 16.8% (8.7–32.3); and 21.1% (10.2–43.9), respectively (repeated-measures ANOVA, p<0.02 (Dunnett's post hoc: control vs tannic acid p<0.05). When 800mg of calcium was added (study B), iron bioavailability was 16.7% (10.1–27.5); 13.2% (7.1–24.6); 14.8% (8.8–25.1); and 12.6% (5.5–28.8), respectively (repeated-measures ANOVA, NS). ConclusionsTannic acid decreases the fasting bioavailability of non-heme iron, however this effect did not exist in the presence of calcium. No effect was observed by phytic acid or citrus pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium.

Negative Effect of Camu-Camu (Myrciaria dubia) Despite High Vitamin C Content on Iron Bioavailability, Using a Caco-2 Cell Model

1. Rice Research for Quality Improvement: Genomics and Genetic Engineering Abdul Rehman, Hafiza Almas, Komal Mazhar, Fazal Akbar, Qasim Ali, Muhammad Azhar, Xiongming Du CrossRef

Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells.

Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55) increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions.

Inclusion of Guava Enhances Non-Heme Iron Bioavailability but Not Fractional Zinc Absorption from a Rice-Based Meal in Adolescents

Assessing the bioavailability of non-heme iron and zinc is essential for recommending diets that meet the increased growth-related demand for these nutrients. We studied the bioavailability of iron and zinc from a rice-based meal in 16 adolescent boys and girls, 13–15 y of age, from 2 government-run residential schools. Participants were given a standardized rice meal (regular) and the same meal with 100 g of guava fruit (modified) with 57Fe on 2 consecutive days. A single oral dose of 58Fe in orange juice was given at a separate time as a reference dose. Zinc absorption was assessed by using 70Zn, administered intravenously, and 67Zn given orally with meals. The mean hemoglobin concentration was similar in girls (129 ± 7.8 g/L) and boys (126 ± 7.1 g/L). There were no sex differences in the indicators of iron and zinc status except for a higher hepcidin concentration in boys (P < 0.05). The regular and modified meals were similar in total iron (10–13 mg/meal) and zinc (2.7 mg/meal) content. The molar ratio of iron to phytic acid was >1:1, but the modified diet had 20 times greater ascorbic acid content. The absorption of 57Fe from the modified meal, compared with regular meal, was significantly (P < 0.05) greater in both girls (23.9 ± 11.2 vs. 9.7 ± 6.5%) and boys (19.2 ± 8.4 vs. 8.6 ± 4.1%). Fractional zinc absorption was similar between the regular and modified meals in both sexes. Hepcidin was found to be a significant predictor of iron absorption (standardized β = −0.63, P = 0.001, R2 = 0.40) from the reference dose. There was no significant effect of sex on iron and zinc bioavailability from meals. We conclude that simultaneous ingestion of guava fruit with a habitual rice-based meal enhances iron bioavailability in adolescents.

Involvement of polyamines in iron(III) transport in human intestinal Caco-2 cell lines

Natural polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm), which are present in the human diet in large amounts, associated with their active transporter, are assumed to play a role in non-heme iron uptake and iron bioavailability from nutrients. Enterocytes and hepatocytes play pivotal roles in the regulation of body iron homeostasis. In this study, we report the effects of natural polyamines on iron transport in the Caco-2 cell line. In enterocyte-like Caco-2 cells, polyamines did not significantly modulate the transepithelial iron flux across the cell monolayer cultured on permeable membranes. In contrast, Spd, Spm, and to a lesser extent, Put were shown to activate Caco-2 cell iron uptake and to induce an increase in the ferritin level. This iron co-transport in enterocytes, which involved an interaction between iron and polyamine then cell uptake of the polyamine-iron complexes by the polyamine transport system, was more pronounced in proliferating than in differentiated Caco-2 cells. Moreover, it was observed at physiological concentrations of both polyamines and iron. It could thus play a role in the rapid renewal of enterocytes. These data suggest the involvement of polyamines as components of the pool of transferrin-independent iron-chelating vectors. Further investigations are needed to demonstrate their biological relevance in physiological situations.

Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron status

Bioavailability of nonheme iron is influenced by the concentration of inhibitors and enhancers in the diet. The fructans inulin and oligofructose have been shown to improve iron absorption in animals through colonic uptake, but this has not been confirmed in humans. The aim of the intervention study was to evaluate the influence of inulin on iron absorption, bifidobacteria, total bacteria, short-chain fatty acids (SCFAs), and fecal pH in women with low iron status (plasma ferritin <25 μg/L). The subjects (n = 32) consumed inulin or placebo 3 times/d (∼20 g/d) for 4 wk, separated by a 2-wk washout period. Iron absorption was measured after 3 wk of inulin and placebo consumption from a standard test meal by using stable-iron-isotope techniques. Fecal bacteria were measured by quantitative polymerase chain reaction, and fecal acids by HPLC. Mean fractional iron absorption in the inulin (15.2%; 95% CI: 8.0%, 28.9%) and placebo (13.3%; 95% CI: 8.1%, 24.3%) periods did not differ significantly (P = 0.10). Inulin decreased fecal pH (P < 0.001) and increased fecal bifidobacteria (P < 0.001) and fecal lactate (P < 0.001) but had no effect on fecal SCFAs and total bacteria. Changes in lactate and acetate concentrations were positively correlated with changes in propionate (P < 0.001) and butyrate (P < 0.02) concentrations, respectively. Iron absorption correlated with fecal pH in the placebo period (P < 0.01) but not in the inulin period (P = 0.37). Although inulin showed prebiotic activity, we were unable to show an increase in iron absorption in women with low iron status. This trial was registered at clinicaltrials.gov as NCT0148309.