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9 pages, 420 KiB

Open AccessArticle

Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis

by Lorenzo Bertani, Domenico Tricò, Federico Zanzi, Giovanni Baiano Svizzero, Francesca Coppini, Nicola de Bortoli, Massimo Bellini, Luca Antonioli, Corrado Blandizzi and Santino Marchi

Nutrients 2021, 13(2), 608; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020608 - 12 Feb 2021

Cited by 13 | Viewed by 3896

Abstract

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare [...] Read more.

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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11 pages, 690 KiB

Open AccessArticle

Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial

by Maria Björmsjö, Olle Hernell, Bo Lönnerdal and Staffan K. Berglund

Nutrients 2021, 13(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010003 - 22 Dec 2020

Cited by 14 | Viewed by 3746

Abstract

Many infant formulas are fortified with iron at 8–14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was [...] Read more.

Many infant formulas are fortified with iron at 8–14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf−) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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13 pages, 1472 KiB

Open AccessArticle

Impact of Ascorbic Acid on the In Vitro Iron Bioavailability of a Casein-Based Iron Fortificant

by Magalie Sabatier, Andreas Rytz, Joeska Husny, Stéphane Dubascoux, Marine Nicolas, Anant Dave, Harjinder Singh, Mary Bodis and Raymond P. Glahn

Nutrients 2020, 12(9), 2776; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092776 - 11 Sep 2020

Cited by 19 | Viewed by 3711

Abstract

A new iron–casein complex (ICC) has been developed for iron (Fe) fortification of dairy matrices. The objective was to assess the impact of ascorbic acid (AA) on its in vitro bioavailability in comparison with ferrous sulfate (FeSO₄) and ferric pyrophosphate (FePP). [...] Read more.

A new iron–casein complex (ICC) has been developed for iron (Fe) fortification of dairy matrices. The objective was to assess the impact of ascorbic acid (AA) on its in vitro bioavailability in comparison with ferrous sulfate (FeSO₄) and ferric pyrophosphate (FePP). A simulated digestion coupled with the Caco-2 cell culture model was used in parallel with solubility and dissociation tests. Under diluted acidic conditions, the ICC was as soluble as FeSO₄, but only part of the iron was found to dissociate from the caseins, indicating that the ICC was an iron chelate. The Caco-2 cell results in milk showed that the addition of AA (2:1 molar ratio) enhanced iron uptake from the ICCs and FeSO₄ to a similar level (p = 0.582; p = 0.852) and to a significantly higher level than that from FePP (p < 0.01). This translated into a relative in vitro bioavailability to FeSO₄ of 36% for FePP and 114 and 104% for the two ICCs. Similar results were obtained from water. Increasing the AA to iron molar ratio (4:1 molar ratio) had no additional effect on the ICCs and FePP. However, ICC absorption remained similar to that from FeSO₄ (p = 0.666; p = 0.113), and was still significantly higher than that from FePP (p < 0.003). Therefore, even though iron from ICC does not fully dissociate under gastric digestion, iron uptake suggested that ICCs are absorbed to a similar amount as FeSO₄ in the presence of AA and thus provide an excellent source of iron. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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17 pages, 896 KiB

Open AccessCommunication

Anemia of Chronic Diseases: Wider Diagnostics—Better Treatment?

by Michał Wiciński, Grzegorz Liczner, Karol Cadelski, Tadeusz Kołnierzak, Magdalena Nowaczewska and Bartosz Malinowski

Nutrients 2020, 12(6), 1784; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061784 - 16 Jun 2020

Cited by 43 | Viewed by 15098

Abstract

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is [...] Read more.

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is the second most common type of anemia after iron deficiency anemia in the world. Its severity generally correlates with the severity of the underlying disease. This disease most often coexists with chronic inflammation, autoimmune diseases, cancer, and kidney failure. Before starting treatment, one should undertake in-depth diagnostics, which includes not only assessment of complete blood count and biochemical parameters, but also severity of the underlying disease. The differential diagnosis of anemia of chronic diseases is primarily based on the exclusion of other types of anemia, in particular iron deficiency. The main features of anemia of chronic diseases include mild to moderate lowering of hemoglobin level, decreased percentage of reticulocyte count, low iron and transferrin concentration, but increased ferritin. Due to the increasingly better knowledge of the pathomechanism of chronic diseases and cancer biology, the diagnosis of this anemia is constantly expanding with new biochemical indicators. These include: the concentration of other hematopoietic factors (folic acid, vitamin B₁₂), hepcidin, creatinine and erythropoietin. The basic form of treatment of anemia of chronic diseases remains supplementation with iron, folic acid and vitamin B₁₂ as well as a diet rich in the above-mentioned hematopoietic factors. The route of administration (oral, intramuscular or intravenous) requires careful consideration of the benefits and possible side effects, and assessment of the patient’s clinical status. New methods of treating both the underlying disease and anemia are raising hopes. The novel methods are associated not only with supplementing deficiencies, but also with the administration of drugs molecularly targeted to specific proteins or receptors involved in the development of anemia of chronic diseases. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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12 pages, 2650 KiB

Open AccessArticle

JNK/p66Shc/ITCH Signaling Pathway Mediates Angiotensin II-induced Ferritin Degradation and Labile Iron Pool Increase

by Andżelika Borkowska, Urszula Popowska, Jan Spodnik, Anna Herman-Antosiewicz, Michał Woźniak and Jędrzej Antosiewicz

Nutrients 2020, 12(3), 668; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12030668 - 29 Feb 2020

Cited by 9 | Viewed by 2830

Abstract

Angiotensin II (Ang II) induces deleterious changes in cellular iron metabolism and increases the generation of reactive oxygen species. This leads to an impairment of neuronal and vascular function. However, the mechanism underpinning Ang II-induced changes in iron metabolism is not known. We [...] Read more.

Angiotensin II (Ang II) induces deleterious changes in cellular iron metabolism and increases the generation of reactive oxygen species. This leads to an impairment of neuronal and vascular function. However, the mechanism underpinning Ang II-induced changes in iron metabolism is not known. We hypothesized that Ang II-induced ferritin degradation and an increase in the labile iron pool are mediated by the c-Jun N-terminal kinase (JNK)/p66Shc/ITCH signaling pathway. We show that Ang II treatment induced ferritin degradation in an endothelial cell lines derived from the bovine stem pulmonary artery (CPAE), human umbilical vein endothelial cells (HUVEC), and HT22 neuronal cells. Ferritin degradation was accompanied by an increase in the labile iron pool, as determined by changes in calcein fluorescence. The JNK inhibitor SP600125 abolished Ang II-induced ferritin degradation. Furthermore, the effect of Ang II on ferritin levels was completely abolished in cells transfected with vectors encoding catalytically inactive variants of JNK1 or JNK2. CPAE cells expressing inactive ITCHor p66Shc (substrates of JNK kinases) were completely resistant to Ang II-induced ferritin degradation. These observations suggest that Ang II-induced ferritin degradation and, hence, elevation of the levels of highly reactive iron, are mediated by the JNK/p66Shc/ITCH signaling pathway. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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Review

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18 pages, 3150 KiB

Open AccessReview

Iron-Enriched Nutritional Supplements for the 2030 Pharmacy Shelves

by Giulio Verna, Annamaria Sila, Marina Liso, Mauro Mastronardi, Marcello Chieppa, Hellas Cena and Pietro Campiglia

Nutrients 2021, 13(2), 378; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020378 - 26 Jan 2021

Cited by 16 | Viewed by 5563

Abstract

Iron deficiency (ID) affects people of all ages in many countries. Due to intestinal blood loss and reduced iron absorption, ID is a threat to IBD patients, women, and children the most. Current therapies can efficiently recover normal serum transferrin saturation and hemoglobin [...] Read more.

Iron deficiency (ID) affects people of all ages in many countries. Due to intestinal blood loss and reduced iron absorption, ID is a threat to IBD patients, women, and children the most. Current therapies can efficiently recover normal serum transferrin saturation and hemoglobin concentration but may cause several side effects, including intestinal inflammation. ID patients may benefit from innovative nutritional supplements that may satisfy iron needs without side effects. There is a growing interest in new iron-rich superfoods, like algae and mushrooms, which combine antioxidant and anti-inflammatory properties with iron richness. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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12 pages, 677 KiB

Open AccessReview

Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine^®) and Potential Applications

by Diego Fernández-Lázaro, Juan Mielgo-Ayuso, Alfredo Córdova Martínez and Jesús Seco-Calvo

Nutrients 2020, 12(6), 1886; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061886 - 24 Jun 2020

Cited by 20 | Viewed by 10258

Abstract

Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study [...] Read more.

Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia. Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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17 pages, 1140 KiB

Open AccessReview

The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine

by Matteo Briguglio, Silvana Hrelia, Marco Malaguti, Giovanni Lombardi, Patrizia Riso, Marisa Porrini, Paolo Perazzo and Giuseppe Banfi

Nutrients 2020, 12(6), 1761; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061761 - 12 Jun 2020

Cited by 37 | Viewed by 13223

Abstract

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when [...] Read more.

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today’s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal. Full article

(This article belongs to the Special Issue Dietary Iron for Human Health)

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