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Nutrition for Anemia

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 67956

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Prof. Dr. Javier Diaz-Castro

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Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain
Interests: pregnancy; lactation; nutrition; perinatal nutrition; pregnancy; oxidative stress; antioxidant system; inflammation; physical activity; endocrine function; early programming
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Dear Colleagues,

Iron deficiency is extremely common and is the most widespread nutritional deficiency in the world, therefore any nutritional strategy to overcome this pathology can be of high interest. To more fully understand iron deficiency anemia, consideration must be directed toward concepts of iron supply and demand for the production of erythrocytes. Erythropoiesis-related demands for iron are created by three variables: tissue oxygenation, erythrocyte turnover, and erythrocyte loss from hemorrhage. Anaemia takes place when the levels of Fe decrease or the requirements overcome the contribution of the intake that is provided in the diet, so the Fe storages of the organism are depleted. There is no doubt that the Fe deficiency is the major cause of the great majority of anaemias although other minerals or vitamins can be also responsible of this pathology. The Fe-deficiency anaemia is characterized by low levels of serum Fe and hemoglobin (Hb), reduction of the hematocrit and increased levels of platelets, low percentage of transferrin saturation, decrease of serum ferritin and a drastic increase in total Fe binding capacity. In addition, the chemical properties of Fe render it a potential hazard within the organism in that ferrous Fe can catalyze the production of reactive oxygen species (ROS), which in turn can lead to peroxidation and radical chain reactions with molecular damage. Regulation of ROS levels and oxidative stress is extremely important in erythropoiesis. Starting at the basophilic erythroblast stage, erythroid precursors synthesize large amounts of Hb, which require haem as a prosthetic group. Thus, Fe uptake and homeostasis for haem biosynthesis also increases, potentially generating ROS through the Fenton reaction. On this topic, you are invited to submit proposals for manuscripts that fit the objectives and the topics of this Special Issue.

Prof. Dr. Javier Diaz-Castro
Guest Editor

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Keywords

Iron Homeostasis
Anemia
Iron supplementation
Oxidative stress
Nutrition
Hematological parameters
Biochemical parameters
Erythropoiesis

Published Papers (11 papers)

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14 pages, 1211 KiB

Open AccessArticle

Role of Fermented Goat Milk on Liver Gene and Protein Profiles Related to Iron Metabolism during Anemia Recovery

by Jorge Moreno-Fernandez, María J. M. Alférez, Inmaculada López-Aliaga and Javier Díaz-Castro

Nutrients 2020, 12(5), 1336; https://doi.org/10.3390/nu12051336 - 08 May 2020

Cited by 6 | Viewed by 4159

Abstract

Despite the crucial role of the liver as the central regulator of iron homeostasis, no studies have directly tested the modulation of liver gene and protein expression patterns during iron deficiency instauration and recovery with fermented milks. Fermented goat milk consumption improves the key proteins of intestinal iron metabolism during iron deficiency recovery, enhancing the digestive and metabolic utilization of iron. The aim of this study was to assess the influence of fermented goat or cow milk consumption on liver iron homeostasis during iron-deficiency anemia recovery with normal or iron-overload diets. Analysis included iron status biomarkers, gene and protein expression in hepatocytes. In general, fermented goat milk consumption either with normal or high iron content up-regulated liver DMT1, FPN1 and FTL1 gene expression and DMT1 and FPN1 protein expression. However, HAMP mRNA expression was lower in all groups of animals fed fermented goat milk. Additionally, hepcidin protein expression decreased in control and anemic animals fed fermented goat milk with normal iron content. In conclusion, fermented goat milk potentiates the up-regulation of key genes coding for proteins involved in iron metabolism, such as DMT1, and FPN1, FTL1 and down-regulation of HAMP, playing a key role in enhanced iron repletion during anemia recovery, inducing a physiological adaptation of the liver key genes and proteins coordinated with the fluctuation of the cellular iron levels, favoring whole-body iron homeostasis. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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10 pages, 275 KiB

Open AccessArticle

Is a Gluten-Free Diet Enough to Maintain Correct Micronutrients Status in Young Patients with Celiac Disease?

by Teresa Nestares, Rafael Martín-Masot, Ana Labella, Virginia A. Aparicio, Marta Flor-Alemany, Magdalena López-Frías and José Maldonado

Nutrients 2020, 12(3), 844; https://doi.org/10.3390/nu12030844 - 21 Mar 2020

Cited by 25 | Viewed by 4214

Abstract

The current study assesses whether the use of a gluten-free diet (GFD) is sufficient for maintaining correct iron status in children with celiac disease (CD). The study included 101 children. The celiac group (n = 68) included children with CD, with long (> 6 months) (n = 47) or recent (< 6 months) (n = 21) adherence to a GFD. The control group (n = 43) included healthy children. Dietary assessment was performed by a food frequency questionnaire and a 3-day food record. Celiac children had lower iron intake than controls, especially at the beginning of GFD (p < 0.01). The group CD-GFD >6 months showed a higher intake of cobalamin, meat derivatives and fish compared to that of CD-GFD <6 months (all, p < 0.05). The control group showed a higher consumption of folate, iron, magnesium, selenium and meat derivatives than that of children CD-GFD >6 months (all, p < 0.05). Control children also showed a higher consumption of folate and iron compared to that of children CD-GFD <6 months (both, p < 0.05). The diet of celiac children was nutritionally less balanced than that of the control. Participation of dietitians is necessary in the management of CD to guide the GFD as well as assess the inclusion of iron supplementation and other micronutrients that may be deficient. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

13 pages, 561 KiB

Open AccessArticle

Adjusting Haemoglobin Values for Altitude Maximizes Combined Sensitivity and Specificity to Detect Iron Deficiency among Women of Reproductive Age in Johannesburg, South Africa

by Takana Mary Silubonde, Jeannine Baumgartner, Lisa Jayne Ware, Linda Malan, Cornelius Mattheus Smuts and Shane Norris

Nutrients 2020, 12(3), 633; https://doi.org/10.3390/nu12030633 - 27 Feb 2020

Cited by 10 | Viewed by 2993

Abstract

In South Africa, haemoglobin (Hb) is measured to screen for iron deficiency (ID). However, low levels of Hb are only a late stage indicator of ID. Furthermore, Hb values are generally not adjusted for altitude even though recommended by WHO. We determined the Hb threshold with the highest combined sensitivity and specificity for detecting ID among South African women living at 1700 m above sea level. In a cross-sectional study of 492 18–25-year-old women, we measured Hb and iron status biomarkers. Using receiver operating characteristic curves, we determined the Hb threshold with maximum Youden Index for detecting ID. This threshold of <12.35 g/dL resulted in a 37.2% anaemia prevalence (20.9% IDA), and sensitivity and specificity of 55.7% and 73.9%, respectively. The WHO altitude-adjusted threshold of <12.5 g/dL resulted in a 39% anaemia prevalence (21.3% IDA), and sensitivity and specificity of 56.8% and 70.8%, respectively. In contrast, using the unadjusted Hb cut-off of <12 g/dL resulted in a 18.5% anaemia prevalence (12.6% IDA), and sensitivity and specificity of 35.1% and 88.6%, respectively. In this sample of South African women of reproductive age an Hb threshold <12.35 g/dL had the highest combined sensitivity and specificity for detecting ID. The diagnostic performance of this Receiver operating characteristic curve-determined threshold was comparable to the altitude-adjusted threshold proposed by WHO. Thus, clinical and public health practice in South Africa should adopt adjustment of Hb for altitude to avoid underestimation of ID and missing women in need for intervention. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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9 pages, 847 KiB

Open AccessArticle

Acai Extract Transiently Upregulates Erythropoietin by Inducing a Renal Hypoxic Condition in Mice

by Shuichi Shibuya, Toshihiko Toda, Yusuke Ozawa, Mario Jose Villegas Yata and Takahiko Shimizu

Nutrients 2020, 12(2), 533; https://doi.org/10.3390/nu12020533 - 19 Feb 2020

Cited by 5 | Viewed by 6667

Abstract

Acai (Euterpe oleracea Mart. Palmae, Arecaceae) is a palm plant native to the Brazilian Amazon. It contains many nutrients, such as polyphenols, iron, vitamin E, and unsaturated fatty acids, so in recent years, many of the antioxidant and anti-inflammatory effects of acai have been reported. However, the effects of acai on hematopoiesis have not been investigated yet. In the present study, we administered acai extract to mice and evaluated its hematopoietic effects. Acai treatment significantly increased the erythrocytes, hemoglobin, and hematocrit contents compared to controls for four days. Then, we examined the hematopoietic-related markers following a single injection. Acai administration significantly increased the levels of the hematopoietic-related hormone erythropoietin in blood compared to controls and also transiently upregulated the gene expression of Epo in the kidney. Furthermore, in the mice treated with acai extract, the kidneys were positively stained with the hypoxic probe pimonidazole in comparison to the controls. These results demonstrated that acai increases the erythropoietin expression via hypoxic action in the kidney. Acai can be expected to improve motility through hematopoiesis. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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15 pages, 803 KiB

Open AccessArticle

Beneficial Effect of Ubiquinol on Hematological and Inflammatory Signaling during Exercise

by Javier Diaz-Castro, Jorge Moreno-Fernandez, Ignacio Chirosa, Luis Javier Chirosa, Rafael Guisado and Julio J. Ochoa

Nutrients 2020, 12(2), 424; https://doi.org/10.3390/nu12020424 - 06 Feb 2020

Cited by 15 | Viewed by 5084

Abstract

Strenuous exercise (any activity that expends six metabolic equivalents per minute or more causing sensations of fatigue and exhaustion to occur, inducing deleterious effects, affecting negatively different cells), induces muscle damage and hematological changes associated with high production of pro-inflammatory mediators related to muscle damage and sports anemia. The objective of this study was to determine whether short-term oral ubiquinol supplementation can prevent accumulation of inflammatory mediators and hematological impairment associated to strenuous exercise. For this purpose, 100 healthy and well-trained firemen were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol was two identical strenuous exercise tests with rest period between tests of 24 h. Blood samples were collected before supplementation (basal value) (T1), after supplementation (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5). Hematological parameters, pro- and anti-inflammatory cytokines and growth factors were measured. Red blood cells (RBC), hematocrit, hemoglobin, VEGF, NO, EGF, IL-1ra, and IL-10 increased in the ubiquinol group while IL-1, IL-8, and MCP-1 decreased. Ubiquinol supplementation during high intensity exercise could modulate inflammatory signaling, expression of pro-inflammatory, and increasing some anti-inflammatory cytokines. During exercise, RBC, hemoglobin, hematocrit, VEGF, and EGF increased in ubiquinol group, revealing a possible pro-angiogenic effect, improving oxygen supply and exerting a possible protective effect on other physiological alterations. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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12 pages, 735 KiB

Open AccessArticle

Iron Status of Infants in the First Year of Life in Northern Taiwan

by Chiao-Ming Chen, Shu-Ci Mu, Chun-Kuang Shih, Yi-Ling Chen, Li-Yi Tsai, Yung-Ting Kuo, In-Mei Cheong, Mei-Ling Chang, Yi-Chun Chen and Sing-Chung Li

Nutrients 2020, 12(1), 139; https://doi.org/10.3390/nu12010139 - 03 Jan 2020

Cited by 15 | Viewed by 5282

Abstract

Iron deficiency (ID) and iron deficiency anemia (IDA) typically occur in developing countries. Notably, ID and IDA can affect an infant’s emotion, cognition, and development. Breast milk is considered the best food for infants. However, recent studies have indicated that breastfeeding for more than six months increases the risk of ID. This study investigated the prevalence of ID and IDA, as well as the association between feeding type and iron nutritional status in northern Taiwan. A cross-sectional study was conducted on infants who returned to the well-baby clinic for routine examination from October 2012 to January 2014. Overall, 509 infants aged 1–12 months completed the iron nutritional status analysis, anthropometric measurement, and dietary intake assessment, including milk and complementary foods. The results revealed that 49 (10%) and 21 (4%) infants in their first year of life had ID and IDA, respectively, based on the World Health Organization criteria. Breastfed infants had a higher prevalence rate of ID and IDA than mixed-fed and formula-fed infants (p < 0.001). Regarding biomarkers of iron status, plasma hemoglobin (Hb), ferritin, and transferrin saturation (%) levels were significantly lower in ID and IDA groups. The prevalence of ID and IDA were 3.7% and 2.7%, respectively, in infants under six months of age, but increased to 20.4% and 6.6%, respectively, in infants above six months of age. The healthy group had a higher total iron intake than ID and IDA groups, mainly derived from infant formula. The total dietary iron intake was positively correlated with infants’ Hb levels. Compared with formula-fed infants, the logistic regression revealed that the odds ratio for ID was 2.157 (95% confidence interval [CI]: 1.369–3.399) and that for IDA was 4.196 (95% CI: 1.780–9.887) among breastfed infants (p < 0.001) after adjusted for all confounding factors (including gestational week, birthweight, sex, body weight percentile, body length percentile, age of infants, mothers’ BMI, gestational weight gain, education level, and hemoglobin level before delivery). In conclusion, our results determined that breastfeeding was associated with an increased the prevalence of ID and/or IDA, especially in infants above six months. This suggests that mothers who prolonged breastfeed after six months could provide high-quality iron-rich foods to reduce the prevalence of ID and IDA. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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19 pages, 974 KiB

Open AccessArticle

The Effectiveness of Different Doses of Iron Supplementation and the Prenatal Determinants of Maternal Iron Status in Pregnant Spanish Women: ECLIPSES Study

by Lucía Iglesias Vázquez, Victoria Arija, Núria Aranda, Estefanía Aparicio, Núria Serrat, Francesc Fargas, Francisca Ruiz, Meritxell Pallejà, Pilar Coronel, Mercedes Gimeno and Josep Basora

Nutrients 2019, 11(10), 2418; https://doi.org/10.3390/nu11102418 - 10 Oct 2019

Cited by 17 | Viewed by 7181

Abstract

Iron deficiency (ID), anemia, iron deficiency anemia (IDA) and excess iron (hemoconcentration) harm maternal–fetal health. We evaluated the effectiveness of different doses of iron supplementation adjusted for the initial levels of hemoglobin (Hb) on maternal iron status and described some associated prenatal determinants. The ECLIPSES study included 791 women, randomized into two groups: Stratum 1 (Hb = 110–130g/L, received 40 or 80mg iron daily) and Stratum 2 (Hb > 130g/L, received 20 or 40mg iron daily). Clinical, biochemical, and genetic information was collected during pregnancy, as were lifestyle and sociodemographic characteristics. In Stratum 1, using 80 mg/d instead of 40 mg/d protected against ID on week 36. Only women with ID on week 12 benefited from the protection against anemia and IDA by increasing Hb levels. In Stratum 2, using 20 mg/d instead of 40 mg/d reduced the risk of hemoconcentration in women with initial serum ferritin (SF) ≥ 15 μg/L, while 40 mg/d improved SF levels on week 36 in women with ID in early pregnancy. Mutations in the HFE gene increased the risk of hemoconcentration. Iron supplementation should be adjusted to early pregnancy levels of Hb and iron stores. Mutations of the HFE gene should be evaluated in women with high Hb levels in early pregnancy. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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14 pages, 584 KiB

Open AccessArticle

Fermented Goat Milk Consumption Enhances Brain Molecular Functions during Iron Deficiency Anemia Recovery

by Jorge Moreno-Fernández, Inmaculada López-Aliaga, María García-Burgos, María J.M. Alférez and Javier Díaz-Castro

Nutrients 2019, 11(10), 2394; https://doi.org/10.3390/nu11102394 - 07 Oct 2019

Cited by 6 | Viewed by 5064

Abstract

Iron deficiency anemia (IDA) is one of the most prevalent nutritional deficiencies worldwide. Iron plays critical roles in nervous system development and cognition. Despite the known detrimental consequences of IDA on cognition, available studies do not provide molecular mechanisms elucidating the role of iron in brain functions during iron deficiency and recovery with dairy components. In this study, 100 male Wistar rats were placed on a pre-experimental period of 40 days and randomly divided in two groups: a control group receiving a normal-Fe diet, (45 mg/kg), and an Fe-deficient group receiving a low-Fe diet (5 mg/kg). At day 40, 10 rats per group were sacrificed to anemia control, and 80 rats were divided into eight experimental groups fed with fermented goat or cow milk-based diets, with normal Fe content or Fe overload (450 mg/kg) for 30 days. IDA decreased most of the parameters related to brain molecular functions, namely dopamine, irisin, MAO-A, oxytocin, β-endorphin, and α-MSH, while it increased synaptophysin. These alterations result in an impairment of brain molecular functions. In general, during anemia recovery, fermented goat milk diet consumption increased dopamine, oxytocin, serotonin, synaptophysin, and α-MSH, and decreased MAO-A and MAO-B, suggesting a potential neuroprotective effect in brain functions, which could enhance brain molecular functions. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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21 pages, 1046 KiB

Open AccessReview

Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns

by Genny Raffaeli, Francesca Manzoni, Valeria Cortesi, Giacomo Cavallaro, Fabio Mosca and Stefano Ghirardello

Nutrients 2020, 12(6), 1554; https://doi.org/10.3390/nu12061554 - 27 May 2020

Cited by 27 | Viewed by 5994

Abstract

Iron is an essential micronutrient for early development, being involved in several cellular processes and playing a significant role in neurodevelopment. Prematurity may impact on iron homeostasis in different ways. On the one hand, more than half of preterm infants develop iron deficiency (ID)/ID anemia (IDA), due to the shorter duration of pregnancy, early postnatal growth, insufficient erythropoiesis, and phlebotomy losses. On the other hand, the sickest patients are exposed to erythrocytes transfusions, increasing the risk of iron overload under conditions of impaired antioxidant capacity. Prevention of iron shortage through placental transfusion, blood-sparing practices for laboratory assessments, and iron supplementation is the first frontier in the management of anemia in preterm infants. The American Academy of Pediatrics recommends the administration of 2 mg/kg/day of oral elemental iron to human milk-fed preterm infants from one month of age to prevent ID. To date, there is no consensus on the type of iron preparations, dosages, or starting time of administration to meet optimal cost-efficacy and safety measures. We will identify the main determinants of iron homeostasis in premature infants, elaborate on iron-mediated redox unbalance, and highlight areas for further research to tailor the management of iron metabolism. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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15 pages, 768 KiB

Open AccessFeature PaperReview

Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review

by Rafael Martín-Masot, Maria Teresa Nestares, Javier Diaz-Castro, Inmaculada López-Aliaga, Maria Jose Muñoz Alférez, Jorge Moreno-Fernandez and José Maldonado

Nutrients 2019, 11(11), 2557; https://doi.org/10.3390/nu11112557 - 23 Oct 2019

Cited by 46 | Viewed by 8397

Abstract

Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B₁₂, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B₁₂ deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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23 pages, 982 KiB

Open AccessReview

Anemia of Inflammation with An Emphasis on Chronic Kidney Disease

by Sajidah Begum and Gladys O. Latunde-Dada

Nutrients 2019, 11(10), 2424; https://doi.org/10.3390/nu11102424 - 11 Oct 2019

Cited by 31 | Viewed by 11386

Abstract

Iron is vital for a vast variety of cellular processes and its homeostasis is strictly controlled and regulated. Nevertheless, disorders of iron metabolism are diverse and can be caused by insufficiency, overload or iron mal-distribution in tissues. Iron deficiency (ID) progresses to iron-deficiency anemia (IDA) after iron stores are depleted. Inflammation is of diverse etiology in anemia of chronic disease (ACD). It results in serum hypoferremia and tissue hyperferritinemia, which are caused by elevated serum hepcidin levels, and this underlies the onset of functional iron-deficiency anemia. Inflammation is also inhibitory to erythropoietin function and may directly increase hepcidin level, which influences iron metabolism. Consequently, immune responses orchestrate iron metabolism, aggravate iron sequestration and, ultimately, impair the processes of erythropoiesis. Hence, functional iron-deficiency anemia is a risk factor for several ailments, disorders and diseases. Therefore, therapeutic strategies depend on the symptoms, severity, comorbidities and the associated risk factors of anemia. Oral iron supplements can be employed to treat ID and mild anemia particularly, when gastrointestinal intolerance is minimal. Intravenous (IV) iron is the option in moderate and severe anemic conditions, for patients with compromised intestinal integrity, or when oral iron is refractory. Erythropoietin (EPO) is used to treat functional iron deficiency, and blood transfusion is restricted to refractory patients or in life-threatening emergency situations. Despite these interventions, many patients remain anemic and do not respond to conventional treatment approaches. However, various novel therapies are being developed to treat persistent anemia in patients. Full article

(This article belongs to the Special Issue Nutrition for Anemia)

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