Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Prebiotic Galacto-Oligosaccharides and Fructo-Oligosaccharides, but Not Acacia Gum, Increase Iron Absorption from a Single High-Dose Ferrous Fumarate Supplement in Iron-Depleted Women.

BACKGROUND: Prebiotic galacto-oligosaccharides (GOS) increase iron absorption from fortification-level iron doses given as ferrous fumarate (FeFum) in women and children. Whether GOS or other fibers, such as prebiotic fructo-oligosaccharides (FOS) and acacia gum, increase iron absorption from higher supplemental doses of FeFum is unclear. OBJECTIVES: In iron-depleted [serum ferritin (SF) <25 µg/L] women, we tested if oral coadministration of 15 g GOS, FOS, or acacia gum increased iron absorption from a 100 mg Fe supplement given as FeFum. METHODS: In a randomized, single-blind, crossover study, 30 women (median age: 26.2 y; median SF: 12.9 µg/L) consumed a 100 mg Fe tablet labeled with 4 mg 57Fe or 58Fe, given with either 1) 15 g GOS; 2) 15 g FOS; 3) 15 g acacia gum; or 4) 6.1 g lactose and 1.5 g sucrose (control; matching the amounts of sucrose and lactose present in the GOS powder providing 15 g GOS), dissolved in water. The primary outcome, fractional iron absorption (FIA), was assessed by erythrocyte isotopic incorporation 14 d after administration. Data were analyzed using a linear mixed-effect model. We also tested, in vitro, iron solubility at different pH and dialyzability from the different supplement combinations administered in vivo. RESULTS: FIA from FeFum given with GOS and FOS was significantly higher (+45% and +51%, respectively; P < 0.001 for both) than control; median [IQR] total iron absorption was 34.6 mg [28.4-49.1 mg], 36.1 mg [29.0-46.2 mg], and 23.9 mg [20.5-34.0 mg], respectively. Acacia gum did not significantly affect FIA from FeFum (P = 0.688). In vitro, iron dialyzability of FeFum + GOS was 46% higher than that of FeFum alone (P = 0.003). CONCLUSIONS: In iron-depleted women, both GOS and FOS coadministration with FeFum increased iron absorption by ∼50% from a 100 mg oral iron dose, resulting in an additional 10-12 mg of absorbed iron. Thus, GOS and FOS may be promising new enhancers of supplemental iron absorption.This trial was registered at clinicaltrials.gov as NCT04194255.

Prebiotic Galacto-Oligosaccharides and Fructo-Oligosaccharides, but Not Acacia Gum, Increase Iron Absorption from a Single High-Dose Ferrous Fumarate Supplement in Iron-Depleted Women.

BACKGROUND: Prebiotic galacto-oligosaccharides (GOS) increase iron absorption from fortification-level iron doses given as ferrous fumarate (FeFum) in women and children. Whether GOS or other fibers, such as prebiotic fructo-oligosaccharides (FOS) and acacia gum, increase iron absorption from higher supplemental doses of FeFum is unclear. OBJECTIVES: In iron-depleted [serum ferritin (SF) <25 µg/L] women, we tested if oral coadministration of 15 g GOS, FOS, or acacia gum increased iron absorption from a 100 mg Fe supplement given as FeFum. METHODS: In a randomized, single-blind, crossover study, 30 women (median age: 26.2 y; median SF: 12.9 µg/L) consumed a 100 mg Fe tablet labeled with 4 mg 57Fe or 58Fe, given with either 1) 15 g GOS; 2) 15 g FOS; 3) 15 g acacia gum; or 4) 6.1 g lactose and 1.5 g sucrose (control; matching the amounts of sucrose and lactose present in the GOS powder providing 15 g GOS), dissolved in water. The primary outcome, fractional iron absorption (FIA), was assessed by erythrocyte isotopic incorporation 14 d after administration. Data were analyzed using a linear mixed-effect model. We also tested, in vitro, iron solubility at different pH and dialyzability from the different supplement combinations administered in vivo. RESULTS: FIA from FeFum given with GOS and FOS was significantly higher (+45% and +51%, respectively; P < 0.001 for both) than control; median [IQR] total iron absorption was 34.6 mg [28.4-49.1 mg], 36.1 mg [29.0-46.2 mg], and 23.9 mg [20.5-34.0 mg], respectively. Acacia gum did not significantly affect FIA from FeFum (P = 0.688). In vitro, iron dialyzability of FeFum + GOS was 46% higher than that of FeFum alone (P = 0.003). CONCLUSIONS: In iron-depleted women, both GOS and FOS coadministration with FeFum increased iron absorption by ∼50% from a 100 mg oral iron dose, resulting in an additional 10-12 mg of absorbed iron. Thus, GOS and FOS may be promising new enhancers of supplemental iron absorption. This trial was registered at clinicaltrials.gov as NCT04194255.

Iron Bioavailability from Infant Cereals Containing Whole Grains and Pulses: A Stable Isotope Study in Malawian Children.

BACKGROUND: Compared with infant cereals based on refined grains, an infant cereal containing whole grains (WGs) and pulses with adequate amounts of ascorbic acid to protect against absorption inhibitors could be a healthier source of well-absorbed iron. However, iron absorption from such cereals is uncertain. OBJECTIVE: We measured iron bioavailability from ferrous fumarate (Fefum) added to commercial infant cereals containing 1) refined wheat flour (reference meal), 2) WG wheat and lentil flour (WG-wheat-lentil), 3) WG wheat and chickpea flour (WG-wheat-chickpeas), and 4) WG oat flour (WG-oat) and from ferrous bisglycinate (FeBG) added to the same oat-based cereal (WG-oat-FeBG). METHODS: In a prospective, single-blinded randomized crossover study, 6- to 14-mo-old Malawian children (n = 30) consumed 25-g servings of all 5 test meals containing 2.25 mg stable isotope-labeled iron and 13.5 mg ascorbic acid. Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of isotopes after 14 d. Comparisons were made using linear mixed models. RESULTS: Seventy percent of the children were anemic and 67% were iron deficient. Geometric mean FIA percentages (-SD, +SD) from the cereals were as follows: 1) refined wheat, 12.1 (4.8, 30.6); 2) WG-wheat-lentil, 15.8 (6.6, 37.6); 3) WG-wheat-chickpeas, 12.8 (5.5, 29.8); and 4) WG-oat, 9.2 (3.9, 21.5) and 7.4 (2.9, 18.9) from WG-oat-FeBG. Meal predicted FIA (P ≤ 0.001), whereas in pairwise comparisons, only WG-oat-FeBG was significantly different compared with the refined wheat meal (P = 0.02). In addition, FIAs from WG-wheat-lentil and WG-wheat-chickpeas were significantly higher than from WG-oat (P = 0.002 and P = 0.04, respectively) and WG-oat-FeBG (P < 0.001 and P = 0.004, respectively). CONCLUSION: In Malawian children, when given with ascorbic acid at a molar ratio of 2:1, iron bioavailability from Fefum-fortified infant cereals containing WG wheat and pulses is ≈13-15%, whereas that from FeBG- and Fefum-fortified infant cereals based on WG oats is ≈7-9%.

Acute Consumption of Prebiotic Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate, but not from Ferrous Sulfate and Ferric Pyrophosphate: Stable Iron Isotope Studies in Iron-Depleted Young Women.

BACKGROUND: Although acute consumption of high doses of prebiotic galacto-oligosaccharides (GOS) increases fractional iron absorption (FIA) from ferrous fumarate (FeFum), it is uncertain if low doses of GOS have this effect. Furthermore, whether GOS improve iron absorption from other commonly used iron compounds and whether ascorbic acid (AA) enhances the effect of GOS on iron absorption from FeFum is unclear. OBJECTIVES: In iron-depleted women [serum ferritin (SF) <30 µg/L], we assessed: 1) whether the acute enhancing effect of GOS on FeFum is dose dependent; 2) if GOS would affect FIA from ferrous sulfate (FeSO4) or ferric pyrophosphate (FePP); and 3) if AA and GOS given together enhance FIA from FeFum to a greater extent compared with GOS alone. METHODS: We recruited 46 women (mean age 22.0 y, mean BMI 21.3 kg/m2, median SF 17.1 µg/L), and measured FIA from 14 mg iron labeled with stable isotopes in the following conditions: 1) FIA from FeFum given with 3.5 g, 7 g GOS, and without GOS; 2) FIA from FeSO4 and FePP given with and without 15 g GOS; and 3) FIA from FeFum given with 7 g GOS with and without 93 mg AA. FIA was measured as erythrocyte incorporation of stable isotopes after 14 d. Comparisons were made using paired samples t-test or Wilcoxon rank sum test where appropriate. RESULTS: Giving 7 g of GOS significantly increased FIA from FeFum (+26%; P = 0.039), whereas 3.5 g GOS did not (P = 0.130). GOS did not significantly increase FIA from FeSO4 (P = 0.998) or FePP (P = 0.059). FIA from FeFum given with GOS and AA was significantly higher compared with FeFum given with GOS alone (+30%; P <0.001). CONCLUSIONS: In iron-depleted women, GOS does not increase FIA from FeSO4 or FePP, but it increases FIA from FeFum. Thus, a combination of FeFum and GOS may be a well-absorbed formula for iron supplements. The study was registered at clinicaltrials.gov as NCT03762148.

Consumption of Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate: A Stable Iron Isotope Study in Iron-Depleted Young Women.

BACKGROUND: Animal studies suggest prebiotics can increase iron absorption, but results from human studies are equivocal. OBJECTIVES: In iron-depleted women, before (baseline) and after daily consumption of galacto-oligosaccharides (GOS) for 4 wk, we sought to assess fractional iron absorption (FIA) from an iron supplement given with and without single doses of GOS in test meals or water. METHODS: In all women (n = 34; median serum ferritin concentration = 16.4 µg/L), FIA from doses of 14 mg iron labeled with stable isotopes was measured in the following conditions at baseline: 1) FIA from ferrous fumarate (FeFum) in water given with and without 15 g GOS; 2) FIA from FeFum in a test meal given with and without 15 g GOS; 3) FIA from ferrous sulfate (FeSO4) in a test meal given without 15 g GOS. All subjects then consumed âˆ¼15 g GOS daily for 4 wk. Then the following conditions were tested: 4) FIA from FeFum in a test meal with and without 15 g GOS; and 5) FIA from FeSO4 in a test meal with 15 g GOS. FIA was measured as erythrocyte incorporation of stable isotopes. RESULTS: At baseline, GOS significantly increased FIA from FeFum when given with water (+61%; P < 0.001) and the meal (+28%; P = 0.002). After 4 wk of GOS consumption, GOS again significantly increased FIA from FeFum in the meal (+29%; P = 0.044). However, compared with baseline, consumption of GOS for 4 wk did not significantly enhance absorption from FeFum in the meal given without GOS. FIA from FeSO4 given with GOS in a meal after 4 wk of GOS consumption was not significantly greater than FIA from FeSO4 in a meal without GOS at baseline. CONCLUSIONS: In iron-depleted women, GOS given with FeFum increases FIA, but 4 wk of GOS consumption did not enhance this effect. The study was registered at clinicaltrials.gov as NCT03325270.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Clinical efficacy of Amalaki Rasayana in the management of Pandu (Iron deficiency anemia).

INTRODUCTION: Iron deficiency anemia (IDA) is one of the most common nutritional deficiencies worldwide, which can be correlated to Pandu described in ayurvedic classics. Poor absorption of iron is one of the main reasons of IDA. Amalaki (Phyllanthus emblica L.) has Tridoshahara, especially Pittashamaka (pacifying Pitta) and Rasayana (rejuvenative) properties, thus nourishes the Dhatus and is also known to enhance the absorption of iron. AIMS: To evaluate the efficacy of Amalaki Rasayana in the management of Pandu w.s.r. IDA. MATERIALS AND METHODS: A randomized controlled open clinical trial was conducted at Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar. Iron deficient anemic patients (n = 25) having Hb <12g% in females and 13g% in males and S.Iron <50mg/dl were selected and divided into two groups. Group A was given 2 g of Amalaki Rasayana thrice a day with unequal quantity of honey and ghee for 45 days, while Group B was given 150 mg ferrous fumarate + 1500 mcg folic acid (standard control) once a day with water for 45 days. Assessment was done on the basis of relief in cardinal symptoms of Pandu and hematological parameters. RESULTS AND CONCLUSION: The formulation showed highly significant relief in Panduta (pallor), Daurbalya (weakness), Shirahshoola (headache), Shrama (fatigue), and Gaurava (heaviness) while statistically significant relief in Aruchi (anorexia) and Pindikodweshtan (leg cramps) was reported. On hematological parameters statistically significant increase was found in mean corpuscular volume and mean corpuscular hemoglobin while on biochemical markers statistically significant decrease was found in total iron binding capacity only. However the formulation was not found as effective as standard control.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects.

All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations. The purpose of this study was to evaluate the effect of calcium and iron supplements on dolutegravir pharmacokinetics and strategies (dose separation and food) to attenuate the effects if significant reductions in dolutegravir exposure were observed. This was an open-label, crossover study that randomized 24 healthy subjects into 1 of 2 cohorts to receive 4 treatments: (1) dolutegravir alone, fasting; (2) dolutegravir with calcium carbonate or ferrous fumarate, fasting; (3) dolutegravir with calcium carbonate or ferrous fumarate with a moderate-fat meal; (4) dolutegravir administered 2 hours before calcium carbonate or ferrous fumarate, fasting. Plasma dolutegravir AUC(0-∞), Cmax , and C24 were reduced by 39%, 37%, and 39%, respectively, when co-administered with calcium carbonate while fasting and were reduced by 54%, 57%, and 56%, respectively, when co-administered with ferrous fumarate while fasting. Dolutegravir administration 2 hours before calcium or iron supplement administration (fasted), as well as administration with a meal, counteracted the effect. Dolutegravir and calcium or iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium or iron supplements.

Carotenoids, but not vitamin A, improve iron uptake and ferritin synthesis by Caco-2 cells from ferrous fumarate and NaFe-EDTA.

Due to the high prevalence of iron and vitamin A deficiencies and to the controversy about the role of vitamin A and carotenoids in iron absorption, the objectives of this study were to evaluate the following: (1) the effect of a molar excess of vitamin A as well as the role of tannic acid on iron uptake by Caco-2 cells; (2) iron uptake and ferritin synthesis in presence of carotenoids without pro-vitamin A activity: lycopene, lutein, and zeaxantin; and (3) iron uptake and ferritin synthesis from ferrous fumarate and NaFe-EDTA. Cells were incubated 1 h at 37 °C in PBS pH 5.5, containing (59) Fe and different iron compounds. Vitamin A, ferrous fumarate, ß-carotene, lycopene, lutein, zeaxantin, and tannic acid were added to evaluate uptake. Ferritin synthesis was measured 24 h after uptake experiments. Vitamin A had no effect on iron uptake by Caco-2 cells, and was significantly lower from NaFe-EDTA than from ferrous fumarate (15.2 ± 2.5 compared with 52.5 ± 8.3 pmol Fe/mg cell protein, respectively). Carotenoids increase uptake up to 50% from fumarate and up to 300% from NaFe-EDTA, since absorption from this compound is low when administered alone. We conclude the following: (1) There was no effect of vitamin A on iron uptake and ferritin synthesis by Caco-2cells. (2) Carotenoids significantly increased iron uptake from ferrous fumarate and NaFe-EDTA, and were capable of partially overcoming the inhibition produced by tannic acid. (3) Iron uptake by Caco-2 cell from NaFe-EDTA was significantly lower compared to other iron compounds, although carotenoids increased and tannic acid inhibited iron uptake comparably to ferrous fumarate.