A Nurse Is Reviewing the Dietary Choices of an Adolescent Who Has Iron Deficiency Anemia

Introduction

Atomic number 26 deficiency anemia is a serious global public wellness problem. As per the Earth Health Organisation (WHO) study, worldwide, 42% of pregnant women, 30% of non-pregnant women (aged 15–50 years), 47% of preschool children (< 5 years), and 12.7% of immature men (> 15 years) are anaemic. Iron deficiency anemia (IDA) adversely affects the growth and cognitive development in children; cerebral, concrete, and psychological health in non-pregnant women, and maternal and neonatal outcomes in pregnant women. Its prevalence amidst women betwixt the ages of 15 and 49 is more than than 40% in most Asian and African countries (one). Many factors crusade IDA including, gut health, dietary iron deficiency, bioavailability, folic acrid deficiency, Vitamin C, Vitamin A, and Vitamin B12 deficiency. In improver, hookworm infestation and malaria also contribute to the increase in the prevalence of IDA amongst Asian and African countries (2).

Three major approaches are followed to command IDA globally, which are supplementation with fe and folic acrid tablets, fortification and natural food-based approaches. Despite the wide implementation of the first two approaches, IDA remains a serious malnutrition problem with an increasing trend globally. The third approach mainly focuses on dietary diversification and enrichment of diets with naturally iron-rich foods without the potential side effects of bogus additives.

In developing countries, milled rice, wheat, and maize replaced the traditional nutritious crops. Refined foods are abundant in starch but lack nutrients, peculiarly micronutrients such equally iron (Fe) and zinc (Zn). Given that a major part (>80%) of the diet in developing countries (3) comprises low iron staple food, achieving sufficient intake of atomic number 26 through the remaining 20% of the nutrition is impractical. Therefore, it is important to diversify the staple food by including naturally iron-rich food crops such equally millets (4). In addition, millets accept a ii.iii to 4.0 times more than dietary fiber (half dozen.four ± 0.6 to 11. five ± 0.6 yard/100g) compared with refined rice and refined wheat (five), which acts equally food for beneficial gut microbiome that improves abundance and alters the gut limerick in a beneficial way (6, 7). Millets take added advantages as they are recognized as a smart nutrient, i.e., not only good for you since it is nutritious and healthy, but besides adept for the planet because it is environmentally sustainable and good for farmers since it is resilient and climate-smart (viii).

Fauna sources of haem iron are well known for their high bioavailability. However, it is non always affordable to the poorest segments of the population. Moreover, a vegetarian population crave alternating plant sources of highly absorbable iron to tackle atomic number 26 deficiency. Although millets are recognized every bit being naturally rich in iron, their nutrient limerick varies with the blazon, variety, and growing atmospheric condition. Commonly used food composition tables while providing an overview of the nutrient composition do not include this particular (v, 9, ten). Presenting a single value for iron level in a type of millet can be misleading as atomic number 26 levels tin can vary significantly amidst varieties. Atomic number 26 levels tin be as much equally triple in a unremarkably available variety over some other.

Non-haem iron (plant-based) is not absorbed equally readily every bit haem iron (animal-based) in the presence of phytate and tannin in millets. Nearly of the cereals such as wheat flour, brown rice, and barley incorporate phytic acid to levels (5) that are far college than that of millets. However, the phytate content of millets is often overly emphasized. All the same, it is important to understand the bioavailability of iron from millets and its impact on anemia status. Although few studies have investigated the bioavailability of iron by in vitro and in vivo methods, not all of them are well known or promoted. Moreover, very few studies focus on the overall beneficial effects of millets on anemia, as nigh studies focus on but ane or just a few of the outcomes, such as hemoglobin, absorbed iron, serum ferritin, and serum transferrin levels. Collating this information can provide information on which millets to use and to what extent they can improve iron condition and the type of processing that can enhance the bioavailability of dietary iron. It is against this background that this systematic review of published scientific studies on millets was undertaken to investigate the range of iron levels and its bioavailability in society to enable a comparison with major staples such as rice, wheat (both whole grain and refined), and maize. This was followed by a meta-assay to collate all the science-based evidence available on millets, their effects on iron status, hemoglobin levels in the torso, and their related power to reduce iron deficiency anemia.

Research Questions

Does consumption of millets-based food help amend iron status and hemoglobin levels and reduce iron deficiency anemia? How does this compare with regular non-millet diets?

Methods

Study Period and Protocol

The systematic review and meta-analysis were conducted from October 2017 to April 2021. The PRISMA checklist was used to write the protocol (xi). The protocol was registered through an online "research registry" with the Unique Identification number "reviewregistry1114".

Search, Inclusion, and Exclusion Criteria

Studies written in English and published between 2010 and 2020 were considered. Google Scholar, Scopus, Web of Scientific discipline, PubMed, and CABI abstruse were used to find studies relevant to the research questions. The search was conducted using the search strategy and keywords (Tabular array ane), which were further screened for relevance to the study, abyss of data and quality of inquiry based on the inclusion and exclusion criteria.

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Tabular array i. Search keywords used to identify relevant papers.

Inclusion Criteria

The following criteria were included: (1) inquiry studies conducted to exam the efficacy of millets in reducing anemia and improving hemoglobin, serum ferritin levels, iron condition, and/or bioavailability of fe; (2) studies that had information on whatsoever or all of the outcomes including levels of hemoglobin, serum ferritin, absorbed iron, and bioavailability of iron; (3) efficacy studies conducted using high iron and/or biofortified varieties of millets; (4) studies conducted on any age group or gender of any population to exam the efficacy of millets in reducing iron deficiency; (five) both in vivo and in vitro studies that assessed the bioavailability of iron, with the two types of studies treated as separate; (six) peer-reviewed journal articles, total MSc or PhD theses submitted to universities, and total research papers from theses if available online.

Exclusion Criteria

Review articles, beast studies, and publications with incomplete data were excluded.

Data Drove

The study used the PRISMA checklist at every step of data collection, extraction, and analysis (Figure 1). Only the relevant papers downloaded that addressed the research questions were used. The references in the relevant publications were too checked by hand search to find more related research articles. If simply an abstract was found relevant to this study, so efforts were made to download open access articles or collect the total paper. Afterwards collecting the full paper, if whatever required information were missing, the authors were contacted, and the full information was requested for utilize in the meta-assay. The data were extracted from the manufactures and documented in Excel sheets. Using the information, descriptive statistics, regression analysis, forest plots, and publication bias analysis were performed.

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Figure 1. PRISMA menses diagram for systematic review.

Data Items

Each study was labeled with details on the author and the year of publication. The historic period grouping and gender of the study participants were recorded, along with the country, study method, sample size, and type and form of millets used. The numerical variables considered for the meta-analysis included mean and standard deviations of levels of hemoglobin, absorbed iron, and serum ferritin. The data were and so entered into an Excel sail as per the guidelines (12, thirteen).

Summary Measures and Issue Synthesis

(one). Pre-and postal service- intervention or (2). test and control diets impact on each effect was recorded with hateful and standard deviation values and used for meta-analysis. Since it is continuous data, a meta-assay was performed to measure out Standardized Mean Departure (SMD) and heterogeneity (itwo). The significance of the results was determined using the fixed-effect model for a single source of data and the random consequence model for other studies. Results from both models were captured in each forest plot. In add-on, descriptive statistics such as mean, standard divergence, and percentage change in hemoglobin levels were calculated for both intervention and command samples. Regression analysis was conducted to test the effects of processing such every bit germination, fermentation, and malting of millets on the bioavailability of atomic number 26. The term 'bioavailability' was used to refer to the percentage of iron in the food that is plainly absorbable based on the in vivo and in vitro protocols used in the studies included in the meta-assay. The term 'bioavailable iron' was used to represent the amount of plainly absorbed iron per 100 g of food, and has been calculated every bit:

Bioavailable iron (mg/100 yard food) = fe concentration in the food (mg/100 chiliad) × % bioavailability/100.

Bioavailable atomic number 26 from millets was so compared with the physiological requirement, which is a requirement for absorbed iron (14). The physiological requirement for various age groups to assess whether the bioavailable fe from millets tin can contribute to the physiological requirement. The physiological requirement of fe was obtained from the recommended dietary allowances book released recently (15) and was calculated based on the supposition that 8% of the iron is captivated from the Estimated Actual Requirement (EAR) (15).

Report Quality Assessment

Using the eight-item Newcastle-Ottawa Calibration (NOS), the quality (16, 17) of each study was assessed by two investigators. Any disagreement was resolved past discussing it with a third reviewer. The researchers also practical the principle stated in the study of (18) to further strengthen quality assessment.

Detailed Data Assay

A total of 22 human being studies were found eligible for the meta-analysis with 3 outcomes namely hemoglobin level (m/dl), serum ferritin (ng/ml) and total fe absorbed (mg/day). Nineteen of these studies (based on diverse types and forms of millets) were used to decide the effects of consumption of millets on hemoglobin levels, while two studies were used to determine the effects on iron absorption, and 4 studies were used to measure the effects on serum ferritin levels (a claret protein that contains iron that is usually tested to indicate the level of fe stored in the body). The iron content of millets was categorized as high if fe content was above 6 mg/100 grand (regardless of biofortification), moderate it was from 3 mg/100 g to vi mg/100 yard, and low if below 3 mg/100 thou. They were compared with the corresponding control samples which were mostly rice or wheat-based regular diets as well as low iron millets. The heterogeneity of samples and overall test results were included in the forest plots. Both the random effect and fixed-effect models were tested and used to interpret the results and SMD (19–22).

A meta-analysis was conducted using R Studio iv.0.iv (2021) (www.rstudio.com) to obtain a forest plot, heterogeneity, overall test furnishings in both stock-still and random effect models, and funnel plots to determine the publication bias (12, 23).

Subgroup Analysis

Based on the type of millet (finger millet, pearl millet, sorghum, and mixed millets), the duration of the report ('short' if <iv months while 'long' if > iv months) and the age of the participants (children, adolescents, and adults) were used for subgroup analysis to assess the effects of consumption of millets on hemoglobin levels.

Chance of Bias Assessment

A funnel plot was used to assess publication bias. Selection, detection, attrition and reporting biases were assessed according to the guidelines provided in the Cochrane handbook for systematic reviews of interventions (24).

Results

Meta-Analysis of Information From Human Studies

There were 22 research papers involving human subjects identified as eligible for the meta-analysis for iii outcomes, namely, hemoglobin levels, serum ferritin levels, and total iron absorbed.

Hemoglobin Level

In that location were 19 studies (25–43) used to conduct the meta-analysis on hemoglobin levels, which showed high heterogeneity (Iii = 87%) and statistical significance (Figure 2). The hemoglobin levels in one,022 individuals (from 19 studies) produced SMD of 1.05 at a 95% confidence interval (CI) ranging from 0.63 to one.46 indicating a pregnant (p < 0.01) overall improvement in hemoglobin levels within the group that had consumed millets for a menstruum ranging from 28 days to 4.v years. On average, there was a 13.2% increase in hemoglobin levels relative to the baseline in the intervention grouping who received millet supplementation which is five times higher compared with only a two.7% increment in hemoglobin levels in the control grouping who did not receive millet supplementation and were consuming regular rice or wheat-based nutrition. Seven studies conducted on adolescents showed an increase in hemoglobin levels from ten.8 ± 1.4 (moderate anemia) to 12.2 ± 1.5 g/dl (normal). The studies that qualified for the meta-analysis used finger millet, pearl millet, sorghum, or mixed millets (kodo, little, and foxtail millets). Amid the nineteen studies, 2 studies used pearl millet which had an atomic number 26 content averaging eight.half dozen mg/100 g (44, 45), while the rest of the studies did not bespeak the iron content of millets used in meal preparation.

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Figure 2. Effect of consuming millets on Hemoglobin level.

Atomic number 26 Absorption

The meta-analysis using two studies (44, 45) that measured fe assimilation showed that bioavailable iron in the study that had used high iron pearl millet (8.2 mg/100 chiliad grain) was significantly (p < 0.01) higher (Effigy three) than in the one that had used low iron millets (< three mg/100 g grain) with SMD of 1.25 and 95% CI of 0.77 and 1.74, respectively. The bioavailable iron was one ± 0.45 mg/twenty-four hours from a dietary iron intake of fourteen.i mg/solar day compared with 0.42 ± 0.27 mg/day from a dietary iron intake of 6.3 mg/day, which is vii.5 ± one.half-dozen % bioavailability.

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Figure iii. Effect of consuming millet based meal on bioavailable atomic number 26 content compared to regular meal.

Serum Ferritin Level

Four studies (33, 35, 36, 46) measured serum ferritin, which was significantly increased in groups consuming high atomic number 26 millet-based meals (Figure iv), compared with low fe millet-based meals or non-millet-based meals (p < 0.01) with moderate heterogeneity among the studies (I2 = 76%) and SMD of 0.59 and 95% CI of 0.13; 1.06.

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Effigy 4. Effect of consuming millet based meal on serum ferritin level.

There was a 54.7% boilerplate increase in serum ferritin levels subsequently the consumption of pearl millet (2 studies), sorghum meals (one study), and teff bread (one study). The average iron level in pearl millet-based meal was 8.2 mg/100 g while it was 5.vi mg/100 thousand in teff breadstuff. The intervention was conducted for vi weeks using teff bread and six months using pearl millet-based meals. The iron levels in sorghum used in the study for 8 months were non indicated.

Meta-Analysis of in-vitro Iron Bioavailability Studies

The meta-analysis included viii studies that measured in vitro atomic number 26 bioavailability in pearl millet and the furnishings of processing. 1 report with two observations (47) showed ii.v mg/100 g bioavailable iron in a high iron pearl millet-based meal, which was significantly higher (p < 0.01) than in the rice-based command meal (0.75 mg/100 g) with a bioavailability per centum of 7.five% and 7.ix%, respectively (Figure five). Similarly, vii in-vitro bioavailability studies showed (48–54), that processing such as formation, fermentation, decortication, expansion (a thermal process that increases the size and volume of the grain) and popping of millet grains had significantly (p < 0.01) increased bioavailable iron than those in unprocessed control millet grain (Effigy 6). The increase in bioavailable iron past fermentation and germination was 3.4 times and 2.2 times college, respectively than in unprocessed millets.

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Figure v. In-vitro bioavailability of iron in millet compared to rice based meal.

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Figure half-dozen. In-vitro bioavailability of iron in millets afterwards processing.

Boosted Statistics

Statistical comparing was conducted to determine the percentage bioavailability of atomic number 26 and bioavailable iron in loftier atomic number 26 pearl millet in two in vivo studies (44, 45) and 11 in vitro studies on pearl millet, finger millet, and sorghum (47–57). The fe content in the millets used in the in vitro studies was 17.27 ± 13.38 mg/100 g. The in-vitro studies also showed a meaning increase in bioavailable iron (mg/100 1000) with the increasing atomic number 26 content of millets (Figure 7). It is besides noted some studies shows high atomic number 26 content in the fermented millets even up to 49.seven mg/100 g (54). On the other manus, based on the ii human studies conducted using iron-rich pearl millet (8.3 mg/100 g) showed the bioavailability of 7.5 ± 1.vi% with bioavailable iron of ane.0 ± 0.4 mg/100 g, while the concentration of atomic number 26 in the entire pearl millet-based meals was xiv.1 ± ix mg/100 k.

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Figure 7. In-vitro bioavailable fe from millets.

Regardless of the iron concentration in millets, the overall per centum bioavailability in millets from human studies was vii.22 ± one.78%, with an overall bioavailable iron content of 0.7 ± 0.45 mg/100 g (Table 2).

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Table 2. Iron bioavailability and bioavailable iron in millets based on the blazon of study (in vitro and in vivo).

In this systematic review, the atomic number 26 content in millets, regardless of biofortification, were organized into low (<3 mg/100 g), moderate (3 to <6 mg/100 yard), and high (6 mg/100 g) categories based on their provisions of >thirty% (high), 15–30% (moderate), and <15% (depression) daily iron requirements for adults. The bioavailability from these categories was assessed. The results showed that meals prepared with high iron millets had high bioavailable atomic number 26 that can provide 100% of the physiological requirement of atomic number 26 as proposed by ICMR (2020) (Table iii). Results from in vivo studies showed that bioavailable atomic number 26 was high in loftier iron millets (ane ± 0.4 mg/100 g), compared with low iron millets (0.4 ± 0.2 mg/100 thou).

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Tabular array three. The effect of processing on the bioavailability of iron in millets and its potential to meet the physiological requirement of fe.

Effects of Processing on the Bioavailability of Iron

Processes such as fermentation, formation, and soaking did not bear upon the total iron content of the grain significantly. Moreover, at that place was significantly higher bioavailable atomic number 26 in these processes compared with that in unprocessed millets (Table three). On the other manus, decortication, popping, and malting reduced the iron content. Still, bioavailable iron was still higher than or equal to that in unprocessed grains.

Millets can provide 100% of the physiological requirement of iron for unlike age groups (45), though this depends on the type, variety, and the kind of processing undergone. Based on the results from in vitro studies, soaking was not significantly associated with an increment in iron bioavailability (Table 3). On the other hand, even if the iron content in millets was low, malting increased bioavailable iron past three.5 times, and thereby bioavailable iron was 1.half-dozen times higher than in unprocessed grains which increased its contribution to the physiological requirement to 1.7 times in adult women (from 39 to 68%). In that location were 17 observations on fermented millets which showed that the fermentation process did non bear upon the atomic number 26 content of grains. However, it increased bioavailable atomic number 26 by up to three.4 times (from 0.5 to 1.seven mg/100 one thousand) and can assistance increase the contribution to the physiological iron requirement by 3.iv times in adult women (from 39 to 143%) (Table iii). Fermentation was found to be superior to germination and malting. Germination increased bioavailable atomic number 26 content by upward to 2.two times compared with unprocessed grains (from 0.5 to i.1 mg/100 g) and helped run across 95% of the physiological requirement in adult women, which is 2.four times higher than in unprocessed grains. Adding an assimilation enhancing agent such as Vitamin C rich food improved the percentage of iron bioavailability by up to 6.8 times (50). Other processes such equally decortication and dephytination using phytase enzyme are industrial processes. While both processes decreased iron content in grains by more than l%, they increased bioavailable iron by two.6 and 1.4 times, respectively, thereby increasing their contribution to the physiological requirement in adult women by two.vii and i.5 times, respectively.

Popping slightly reduced (iii%) the iron content of grains. Withal, it increased bioavailable fe by 3.4 times and thereby increasing its contribution to the physiological requirement by three.seven times. Compared with popping, expansion led to a loss of more than 60% of grain fe content while increasing bioavailable iron by 5.iv times compared with unprocessed grains and thereby increased the % contribution to the physiological requirement by 5.8 times in adult women.

Information technology may exist noted that processing did non have the aforementioned touch on in all the studies, mayhap due to the divergence in the methods used, which needs farther evaluation. Fermentation increased mean bioavailable iron content in millets more than all other processing methods.

Three studies conducted on the furnishings of processing on phytate content showed a reduction in phytate content by 29.7% after formation, 28.ane% after soaking, 30.7% after decortication, and 51% after expansion (Table four). This reduction in phytate content increased the bioavailability of iron in these studies. Decortication increased bioavailable iron content by 160% (0.5 mg/100 g to 1.3 mg/100 m).

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Table 4. The effects of processing on phytate and tannin content in millets (mg/100 g).

Formation of finger millet increased bioavailable atomic number 26 content from 0.4 to 1.3 mg/100 yard and decreased tannin content past 50.4%. In pearl millet, cooking reduced tannin content by 5.ii% (Table four).

Subgroup Analysis past Type of Millet

A subgroup analysis was performed to determine the furnishings of consumption of millets on hemoglobin levels based on the type of millets used in the report (finger millet, pearl millet, mixed millets, and sorghum), the duration of the study ('short' or 'long'), and the age group of the participants (children, adolescents, and adult). It was not possible to carry a subgroup assay based on the iron content of the grains since only three of the 19 studies on the effectiveness of millets on hemoglobin outcome indicated the iron content in millets used. A subgroup assay conducted to study the effects of consuming different types of millets on hemoglobin levels showed no pregnant (Effigy eight) departure due to using any particular blazon of millets (p = 0.48). Finger millet and pearl millet had like effects on hemoglobin levels (p < 0.05). The furnishings of using mixed millets could not exist estimated due to the pocket-sized number of studies.

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Effigy eight. Event of consuming different types of millets on Hemoglobin level.

Run a risk of Bias Assessment

The risk of bias assessment shows major risks coming from blinding of the assessment. As millets take a unique colour, texture, and size it is not possible to bear the study by blinding the sample. All the same, information technology is possible to blind the proportion added and the type of millets included, amongst other things. The sample size in studies was reasonable, ranging from 10 to 133 samples for assessing the impact of millet consumption on hemoglobin levels. Except for two studies, all the studies had more than 10 samples each. The Trim and Fit method were practical to account for the effects of small sample size on studies until the funnel plot became symmetrical (p < 0.0001).

Discussions

This study used the term 'loftier iron millet' to betoken any millet that provides more than 6 mg atomic number 26/100 g of grain. Note that the 4 man interventions investigated were based on biofortified pearl millet. Biofortification is a procedure that increases the concentration of targeted nutrients in crops through convenance technologies and can be a promising, sustainable, and cost-constructive arroyo to combating micronutrient deficiencies (59). The other man studies and in vitro studies used varieties of millets that were commonly available.

All the in vivo human studies (lasting 28 days to 6 months), except 2 studies, used 84 to 300 m of pearl millet or finger millet in the class of a meal: bhakri/flatbread, porridge, or upma (thick porridge prepared by seasoning and adding spices, with or without vegetables). The meal was provided once or twice a day. It diversified the cereal-based main meal by incorporating millets and increased the intake of iron from the principal meal.

Among the 19 studies in the meta-assay to assess the impact on hemoglobin levels, merely 3 studies indicated the levels of fe in millets used. The iron content in the millet grain has a huge touch on bioavailable iron, which in turn impacts the anemia status. It is noteworthy that the consumption of fe-rich pearl millet with 8.3 mg/100 1000 of fe levels contributed more than 50% of atomic number 26 to the entire meal with 14.one ± 9 mg of iron and improved the iron bioavailability with bioavailable iron of 1 ± 0.4 mg/mean solar day, compared with the consumption of a depression iron pearl millet (< iii mg/100 g) repast. Regardless of the percentage of bioavailability of iron, if the millet contains high fe, so the corporeality of bioavailable atomic number 26 also increases. In general, the per centum bioavailability of iron from establish-based food varies from 1 to 10% (lx) and ICMR. (fifteen) also shows that information technology considered viii% bioavailability of fe from cereal-based diets. This shows that compared with many plant-based foods, millets have an equal or better bioavailability percentage.

Still, the same was not the instance in vitro studies, probably because of the variation in the methodology used.

In vitro Methods Used for the Bioavailability Study

Different in-vivo, in-vitro studies showed significant variation in the bioavailability percentage, with high iron millets having a lower average bioavailability percent than moderate and low iron millets. Nonetheless, the bioavailability percent was generally high, averaging 17.64 ± 12.49 in the in vitro studies.

Taking bioavailability percentage into account, bioavailable iron varied significantly past variety and tin can approximately triple the quantity of iron bioavailable, ranging from 0.54 ± 0.21 in depression iron varieties to ane.58 ± 1.24 in loftier iron varieties.

The huge variation in bioavailability percentage may be explained by the heterogeneity of the iv methods adopted in the in vitro studies, which were iron solubility, iron dialysability, HCl-extractability, and gastrointestinal models. The in vitro methods aimed at mimicking the gastric and small abdominal phase involving the use of pepsin and pancreatin in iron solubility, dialysability and gastrointestinal methods. However, the studies of (49, 57) used HCl-extractability, which did not involve the use of pepsin and pancreatin and may have led to underestimation or overestimation since it did not consider the digestion of minerals in two cardinal areas of the gastrointestinal tract, which distinguishes this method from the three others. The three other in-vitro methods likewise differed in the setup and conditions, which may have contributed to the differential outcome. The in vitro written report by (50) used ii approaches in the atomic number 26 solubility method in which the usage of either HCl-pepsin or pepsin-pancreatin on mineral extractability, showed differences in the percentage of bioavailability. The differences can be explained by the endpoint measurements. The HCl-pepsin method measured the iron bioavailability at the end of the gastric phase with pH betwixt 1 and 3 and the pepsin-pancreatin method measured the iron bioavailability at the cease of the minor intestinal phase with pH between 7 and eight. The differences in pH in these ii stages may affect the iron solubility and hence the percentage of bioavailability. However, the authors did not outline the methods clearly. Four studies by (47, 53, 55, 56) used the iron dialysability method which was based on equilibrium dialysis. In the absenteeism of in vivo epithelial uptake, this in vitro method adopted dialysis every bit a physical separation technique whereby a dialysis membrane was used. It is important to notation that the selected molecular cut-off of the dialysis membrane, final pH adjustment, time of incubation, and the method used for fe quantification (colourimetric assay or spectrophotometry) are instrumental for consistency in the results (61). In addition, enzymes' sources, pH and digestion fourth dimension, are also important parameters for standardization and may alter enzyme activities and maybe the results. The studies by (48, 54, 58) used gastrointestinal models and adopted different approaches in terms of simulated digestion fluids which influence the ionic strength and ratio of samples to buffer. The study of (54), adopted a more than contempo standardized static in vitro digestion model proposed past (62) which is useful to compare results of the inter and intra laboratory. Still, data validation betwixt in vitro and in vivo studies may provide information when similar meals and experimental conditions are compared (61). Therefore, in vitro methods are useful screening tools to assess iron bioavailability involving a big number of food samples.

Post-harvest iron fortification of pearl millet (artificial fortification) increases the amount of iron bachelor and can be added in large quantities to increase past 32% the full quantity of iron absorbed compared with naturally loftier atomic number 26 pearl millet (44). However, a feasible and sustainable approach for long-run implementation would exist to release more than loftier atomic number 26 millet varieties compared with whatever other method such as fortification and tablet supplementation. The studies showed that, based on the age group, 75 to 100% of the physiological requirement can be achieved through a standard meal prepared using high iron millets. Information technology is noted that fortified foods take processing difficulties such as higher costs of processing and the use of bogus additives for post-harvest fortification. Given that there are many naturally occurring loftier atomic number 26 millets, it is important to utilise them in efficacy studies to generate more than scientific discipline-based evidence and to enable the formulation of policies that would make them bachelor to farmers and also increase the choices for consumers.

Processing had a pregnant positive impact on the bioavailability of iron (Table 3). Of the household and traditional processing methods, fermentation was found to be superior to all other processes for increasing bioavailable atomic number 26. Of the commercial processing methods, expansion was found to exist superior compared with all other processing methods for increasing bioavailable fe. Mostly, dietary inhibitory factors affect the efficiency of iron absorption (63). The major dietary inhibitory factors for fe absorption in millets are phytates and tannin. Information technology is worth noting that millets have similar or lower levels of these anti-nutrients compared with common staples and legumes (5), which are farther reduced by processing to positively improve the bioavailability of fe. Studies also showed significantly increased iron bioavailability in millets following dissimilar methods of processing. In addition, ascorbate (Vitamin C) in the presence of tannins decreases the chelating properties of tannins and thus increases the bioavailability of atomic number 26 past up to half-dozen.8 times (l). While 1 report showed that germination reduced tannin content by 50%, some other written report revealed a sixfold increase in the bioavailability of iron later the same procedure. The study of (64) demonstrated in in vitro studies that processing eliminated inhibitory factors such as phytates and increased the bioaccessibility of iron. However, in vivo studies are required to ascertain if similar furnishings are accomplished using processed millets.

Considering the nutritional quality of all types of millets and their versatile nature of fitting into popular recipes using rice (iii), replicating these studies with millets will be useful to identify variation in iron bioavailability and its benefits in reducing IDA.

Limitation

Iron contagion of food from post-harvest treatment, storage, and cooking vessels, which could increase the iron content of the grain, was non reported past whatsoever studies included in this systematic review. Nevertheless, it was noted that there have been many studies that do specifically await at or incorporate the impacts of atomic number 26 contamination from external sources on a diversity of unlike foods (65–67). Peculiarly while reporting high fe levels (>10 mg/100 yard), it is important to look at the contagion from an external source (44) to avert inflated data.

Conclusion

The systematic review and meta-analysis showed millets are an excellent source of fe with low-cost potential for reducing iron deficiency anemia. This underlined the demand for policymakers to recognize the right varieties and types of millets rich in fe for use as supplement nutrient to counter the high prevalence of anemia in many countries. Selecting the fe rich millet varieties and developing fe-biofortified millet that can provide additional bioavailable iron could exist a promising approach to combatting IDA. Incorporating millets as a staple beyond Asia and Africa could have the potential to brand a significant impact on IDA. This can also be applicable in communities where millets are traditional foods merely not consumed regularly and admission to alternative foods is express. Information technology tin can as well be concluded that the bioavailability of fe in millets can be further improved through processes such as soaking, formation, decortication, and fermentation which tin serve as an effective strategy to reduce iron deficiency anemia.

Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the respective writer.

Writer Contributions

SA and JK-P: conceptualization. JK-P: resource. SA, JK-P, RKB, SU, and MV: data drove, screening, extraction, and analysis. SA, JK-P, IDG, NLBS, and SU: drafting original manuscript. TL, AR, TWT, KS, DJP, and RKB: disquisitional reviewing of protocol and manuscript and editing. All authors contributed to the article and canonical the submitted version.

Funding

This research was supported financially by the Smart Food endowment fund.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could exist construed every bit a potential conflict of interest.

Publisher's Note

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Acknowledgments

The authors acknowledge Joycelyn M. Boiteau, Partition of Nutritional Sciences, Cornell University, Tata-Cornell Institute for Agronomics and Diet, the United States for reviewing the example and her valuable inputs that contributed significantly to the quality of the written report. Thanks are also due to Dr Colin I Cercamondi, Dr Julia Finkelstein, Dr Jere Haas (Project Investigator of the pearl millet trial) and Mr Amy Fothergill (doctoral student at Cornell University), who provided the data from their studies to support the meta-analysis of iron absorption and hemoglobin levels. Dr Waswa Judith confirmed the usage of finger millet in her study, which is highly appreciated. The authors acknowledge Ms Sitaraman Smitha, ICRISAT, for editing the manuscript.

Supplementary Material

The Supplementary Material for this article can be institute online at: https://www.frontiersin.org/manufactures/10.3389/fnut.2021.725529/full#supplementary-textile

References

1. WHO. Prevalence Of Anemia Among Children Under five Years (2016).

2. Balarajan Y, Ramakrishnan U, Ozaltin E, Sharkar AH, Subramanian SV. Anemia in low-income and middle-income countries. Lancet. (2011) 378:2123–35. doi: 10.1016/S0140-6736(10)62304-5

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Anitha S, Kane-Potaka J, Tsusaka TW, Tripathi D, Upadhyay S, Kavishwar A, et al. Acceptance and bear on of millet-based mid-twenty-four hours meal on the nutritional status of adolescent schoolhouse going children in a peri urban region of Karnataka state in India. Nutrients. (2019) 11:1–16. doi: 10.3390/nu11092077

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Vetriventhan Chiliad, Azevedo VCR, Upadhyaya HD. Genetic and genomic resources, and breeding for accelerating improvement of small millets: current status and future interventions. Nucl. (2020) 63:217–239. doi: ten.1007/s13237-020-00322-three

CrossRef Full Text | Google Scholar

5. Longvah T, Ananthan R, Bhaskarachary G, Venkaiah K. Indian Food Composition Tabular array. Hyderabad: National Institute of Nutrition (2017). p. 578.

Google Scholar

half-dozen. Paganini D, Zimmermann MB. The effects of atomic number 26 fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review. Am J Clin Nutr. (2017) 106:1688S–93. doi: 10.3945/ajcn.117.156067

PubMed Abstract | CrossRef Full Text | Google Scholar

seven. Paganini D, Uyoga MA, Zimmermann MB. Iron fortification of foods for infants and children in low-income countries: effects on the gut microbiome, gut inflammation, and diarrhea. Nutrients. (2016) 8:494. doi: ten.3390/nu8080494

PubMed Abstract | CrossRef Full Text | Google Scholar

ix. Rai KN, Patil HT, Yadav OP, Govindaraj G, Khariwal IS, Cherian B. Dhanshakti-A high-atomic number 26 pearl millet multifariousness. Indian Farming. (2014) 64:32–4.

Google Scholar

10. Vetriventhan M, Upadhyaya Hd, Azevedo VCR, Jayapal VA, Anitha S. Variability and trait-specific accessions for grain yield and nutritional traits in germplasm of little millet (Panicum sumatrense Roth. Ex. Roem. & Schult.). Crop Sci. (2021) 61:2658–79. doi: 10.1002/csc2.20527

CrossRef Full Text | Google Scholar

11. Mohar D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement. Open Med. (2009) 3:e1000097. doi: 10.1371/journal.pmed.1000097

PubMed Abstract | CrossRef Full Text | Google Scholar

13. Atkinson LZ, Cipriani A. How to bear out a literature search for a systematic review: a applied guide. Bjpsych Advances. (2018) 24:74–2. doi: x.1192/bja.2017.3

CrossRef Full Text | Google Scholar

xiv. Beaton GH. Minimum Physiological Requirements And Recommended Dietary Allowances. Joint FAO/WHO/UNU good consultation on energy and protein requirements, Rome 1-eight. (1981).

Google Scholar

15. ICMR. Recommended Dietary Allowances and Estimated Average Requirements. (2020). Hyderabad, India: National Institute of Nutrition. p. ane–319.

xvi. Luchini C, Stubbs B, Solmi 1000, Veronese Due north. Assessing the quality of studies in meta-analyses: advantages and limitations of the newcastle ottawa scale. World J Meta-Anal. (2017) 5:fourscore–4. doi: 10.13105/wjma.v5.i4.80

CrossRef Full Text | Google Scholar

17. Peterson J, Welch V, Losos One thousand, Tugwell P. The newcastle-ottawa scale (nos) for assessing the quality of non-randomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Constitute (2011).

Google Scholar

18. Bell A, Fairbrother M, Jones K. Fixed and random effects models: making an informed choice. Qual Quant. (2019) 53:1051–74. doi: 10.1007/s11135-018-0802-x

CrossRef Full Text | Google Scholar

19. Zlowodzki M, Poolman RW, Kerkhoffs GM, Tornetta P, Bhandari Grand. How to interpret a meta-assay and gauge its value every bit a guide for clinical practice? Acta Orthop. (2007) 78:598–609. doi: 10.1080/17453670710014284

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Higgins JPT, Thomas J, Chandler J, Cumpston One thousand, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions version half-dozen.2 (updated February 2021). Cochrane. (2021). Available online at: www.training.cochrane.org/handbook (accessed April thirteen, 2021)

Google Scholar

25. Singh RM, Fedacko J, Mojto Five, Isaza A, Dewi M, Watanabe South, et al. Effects of millet based functional foods rich diet on coronary risk factors among subjects with diabetes mellitus: a single arm real world observation from infirmary registry. MOJ Public Wellness. (2020) 9:18–25. doi: ten.15406/mojph.2020.09.00318

CrossRef Full Text | Google Scholar

26. Durairaj 1000, Gurumurthy G, Nachimuthu Five, Muniappan K. Balasubramanian, S. Dehulled pocket-sized millets: the promising nutricereals for improving the nutrition of children. Matern Child Nutr. (2019) 15:e12791. doi: x.1111/mcn.12791

PubMed Abstract | CrossRef Total Text | Google Scholar

27. Karkada Southward, Upadhya S, Upadhya Southward, Bhat G. Beneficial result of ragi (finger millet) on haematological parameters, trunk mass index, and scholastic performance amidst anemic adolescent high- schoolhouse girls (AHSG). Compr Child Adolesc Nurs. (2018) one–12. doi: ten.1080/24694193.2018.1440031

PubMed Abstruse | CrossRef Full Text | Google Scholar

28. Singh TS, Goyal Thousand. Bear on of an intervention based on pearl millet ladoo on Hemoglobin status of boyish girls. Research gate. (2014) 1–6.

29. Moharana A, Khosla P, Nayak D, Tripathy P. Effect of finger millet [ragi] ladoo consumption on the level of hemoglobin. Eur J mol clin med. (2020) 7:1018–22.

Google Scholar

30. Singh TS, Goyal M, Sheth Yard. Intervention trials with pearl millet based iron rich ladoo and iron folic acrid (IFA) tablets on hemoglobin status of boyish females in Bikaner city. Ethno Med. (2014) eight:77–82. doi: x.1080/09735070.2014.11886475

CrossRef Total Text | Google Scholar

31. Waswa J, Imungi JK. Efficacy of millet based product on direction of geophagy: a randomized control trial. J Nutrient Nutr Disord. (2014) 3:3–10. doi: x.4172/2324-9323.1000152

CrossRef Full Text | Google Scholar

32. Mamiro PS, Kolsteren PW, Van camp JH, Robertfroid DA, Tatala S, Opsomer Every bit. Processed complementary nutrient does not meliorate growth or hemoglobin status of rural Tanzanian infants from 6-12 months of age in kilosa district, Tanzania. Customs Int Nutr. (2004) 1084–90. doi: 10.1093/jn/134.5.1084

PubMed Abstract | CrossRef Total Text | Google Scholar

33. Prasad MPR, senhur B, Kommi K, Madhari R, Rao MV, Patil JV. Bear on of sorghum supplementation on growth and micronutrient condition of schoolhouse going children in southern India–A randomized trial. Indian J Pediatr. (2015) 42:51–vi.

Google Scholar

34. Anandhi S. Comparative Study TO Assess the Effectiveness of Drumstick Leaves Extract vs Ragi Porridge in Increasing the Level of Hemoglobin Among Women With Fe Deficiency Anemia In Selected Community Area at Kanchipuram Commune. Student thesis submitted to MGR medical Academy, Chennai, Tamil Nadu. (2014). p. 93.

Google Scholar

35. Finkelstein JL, Mehta S, Udipi SA, Ghugre PS, Luna SV, Wenger MJ, et al. A randomized trial of iron-biofortified pearl millet in schoolhouse children in Republic of india. J Nutr. (2015) 145:1576–81. doi: ten.3945/jn.114.208009

PubMed Abstruse | CrossRef Full Text | Google Scholar

36. Scott SP, Murray-Kolb LE, Wenger MJ, Udipi SA, Ghugre PS, Male child Eastward, et al. Cerebral performance in Indian school going adolescents is positively affected past consumption of iron-biofortified pearl millet: a half dozen-month randomized controlled efficacy trial. J Nutr. (2018) 1462–71. doi: 10.1093/jn/nxy113

PubMed Abstract | CrossRef Full Text | Google Scholar

37. Arokiamary Southward, Senthilkumar R, Kanchana Due south. Impact of pearl millet based complementary food on biochemical and cognitive profiles of school children (5-half dozen yr sometime). Eur J Nutr Food Saf. (2020) 12:24–34. doi: 10.9734/ejnfs/2020/v12i730245

CrossRef Full Text | Google Scholar

38. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural nutrition supplemented with low cost locally available foods – I impact on expectant women. The Ind J Nutr Dietet. (1982) nineteen:111–6.

Google Scholar

39. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural diet supplemented with low cost locally available foods – Two Impact on nursing mothers. The Ind J Nutr Dietet. (1983) 20:71–8.

Google Scholar

forty. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural diet supplemented with low cost locally bachelor foods – Iv impact on children studied from birth to pre – school age. The Ind J Nutr Dietet. (1984) 21:115–23.

Google Scholar

41. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural diet supplemented with low cost locally available foods – V bear upon on pre-schoolers followed over a flow of four and a one-half years. The Ind J Nutr Dietet. (1984) 21:153–64.

Google Scholar

42. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural diet supplemented with low cost locally available foods – 6 impact on schoolhouse children. The Ind J Nutr Dietet. (1984) 21:187–93.

Google Scholar

43. Devdas RP, Chandrasekhar U, Bhooma. Nutritional outcomes of a rural diet supplemented with low cost locally bachelor foods – VIII impact on preschool children from a tribal customs. The Ind J Nutr Dietet. (1984) 21:315–21.

Google Scholar

44. Cercamondi CI, Egli IM, Mitchikpe Due east, Tossou F, Zeder C, Hounhouigan JD, et al. Total atomic number 26 absorption by young women from fe-biofortified pearl millet composite meals is double that from regular millet meals only less than that from post-harvest iron-fortified millet meals. J Nutr. (2013) 143:1376–82. doi: 10.3945/jn.113.176826

PubMed Abstruse | CrossRef Full Text | Google Scholar

45. Kodkany BS, Bellad RM, Mahantshetti NS, Westcott JE, Krebs NF, Kemp JF. Biofortification of pearl millet with atomic number 26 and zinc in a randomized controlled trial increases assimilation of these minerals higher up physiologic requirements in young children. J Nutr. (2013) 143:1489–93. doi: x.3945/jn.113.176677

PubMed Abstract | CrossRef Total Text | Google Scholar

46. Alaunyte L, Stojceska V, Plunkett A, Derbyshire E. Dietary iron intervention using a staple nutrient product for improvement of iron status in female runners. J Int Soc Sports Nutr. (2014) xi:1–8. doi: 10.1186/s12970-014-0050-y

PubMed Abstruse | CrossRef Full Text | Google Scholar

47. Agte VV, Gokhale MK, Panikar KM, Chiplonkar SA. Cess of pearl millet vs rice based diets for bioavailability of four trace metals. Found Foods Hum Nutr. (1995) 48:149–58. doi: 10.1007/BF01088311

PubMed Abstract | CrossRef Full Text | Google Scholar

48. Afify AE-MMR, El-Beltagi HS, El-Salam SMAbd, Omran AA. Bioavailability of fe, zinc, phytate and phytase activity during soaking and germination of white sorghum varieties. PLoS ONE. (2011). 6:e25512. doi: 10.1371/journal.pone.0025512

PubMed Abstract | CrossRef Full Text | Google Scholar

49. Sripriya G, Antony U, Chandra TS. Changes in sugar, free amino acids, organic acids, phytate and HCl extractability of minerals during formation and fermentation of finger millet (Eleusine coracana). Nutrient Chem. (1997) 58:345–50. doi: x.1016/S0308-8146(96)00206-3

CrossRef Full Text | Google Scholar

50. Mamiro PRS, Van Camp J, Mwikya SM, Huyghebaert A. In vitro extractability of calcium, iron, and zinc in finger millet and kidney beans during processing. Food Chem Toxicol. (2001) 66:1271–5.

Google Scholar

51. Nour AAM, Sokrab AM, Ahmd IAM, Babiker EE. Supplementation and cooking of pearl millet: change in anti-nutrients, and total minerals content and extractability. Innov Rom Nutrient Biotechnol. (2014) fifteen:9–22.

Google Scholar

52. Platel G, Epieson SW, Srinivasan K. Bioaccessible mineral content of malted finger millet (Eleusine coracana), wheat (Triticum aestivum), and Barley (Hordeum vulgare). J Agric Food Chem. (2010) 58:8100–3. doi: 10.1021/jf100846e

PubMed Abstract | CrossRef Full Text | Google Scholar

53. Krishnan R, Dharmaraj U, Malleshi NG. Influence of decortication, popping and malting on bioaccessibility of calcium, iron, and zinc in finger millet. Food scitechnol. (2012) 48:169–74. doi: 10.1016/j.lwt.2012.03.003

CrossRef Total Text | Google Scholar

54. Gabaza Yard, Abraha HS, Muchuweti Chiliad, Vandamme P, Raes K. Fe and zinc bioaccessibility of fermented maize, sorghum and millets from five locations in Republic of zimbabwe. Food Res Int. (2018) 103:361–70. doi: x.1016/j.foodres.2017.10.047

PubMed Abstruse | CrossRef Full Text | Google Scholar

55. Priya S, Kowsalya South. In-vitro-bioaccessibility of fe and zinc from millet based convenience foods. Int J Adv Eng Res Dev. (2017) four:158–62. doi: 10.1111/j.1365-2621.2001.tb15200.x

CrossRef Full Text

56. Hemalatha S, Platel K, Srinivasan K. Influence of germination and fermentation on bio accessibility of zinc and fe from nutrient grains. Eur J Clin Nutr. (2007) 61:342–eight. doi: x.1038/sj.ejcn.1602524

PubMed Abstruse | CrossRef Full Text | Google Scholar

57. Suma PF, Urooj A. Influence of germination on bioaccessible iron and calcium in pearl millet (Pennisetum typhoideum). J Food Sci Technol. (2014) 51:976–81. doi: 10.1007/s13197-011-0585-eight

PubMed Abstruse | CrossRef Full Text | Google Scholar

58. Lestienne I, Besanc P, Caporiccio B, Lullien-peallerin 5, Treache S. Fe and Zinc in Vitro Availability in Pearl Millet Flours (Pennisetum glaucum) with Varying Phytate, Tannin, and Fiber Contents. J Agri Food Chem. (2005) 53:3240–vii. doi: 10.1021/jf0480593

PubMed Abstract | CrossRef Total Text | Google Scholar

59. Bouis HE, Hotz C, McClafferty B, Meenakshi JV, Pfeiffer WH. Biofortification: a new tool to reduce micronutrient malnutrition. Food Nutr Bull. (2011) 32:S31–41. doi: 10.1177/15648265110321S105

PubMed Abstruse | CrossRef Full Text | Google Scholar

60. Givens DI, Sulaiman NLB, Anitha S. Iron deficiency anemia in Bharat, prevalence, aetiology and solutions: a narrative review. (Unpublished)

61. Aragon IJ, Ortiz D, Pachon H. Comparison betwixt in vitro and in vivo methods to screen fe bioavailability. CyTA J Nutrient. (2012) 10:103–xi. doi: 10.1080/19476337.2011.596283

CrossRef Full Text | Google Scholar

62. Minekus M, Alminger Thousand, Alvito P, Rest Due south, Bohn T, Bourlieu C, et al. Standardized static in vitro digestion method suitable for food – an international consensus. Food Funct. (2014) v:1113–24. doi: 10.1039/C3FO60702J

PubMed Abstruse | CrossRef Full Text | Google Scholar

63. Chiplonkar SA, Agte VV. Statistical model for predicting non-heme iron bioavailability from vegetarian meals. Int J Nutrient Sci Nutr. (2006) 57:434–50. doi: 10.1080/09637480600836833

PubMed Abstract | CrossRef Full Text | Google Scholar

64. Abdalla AA, Ahmed IA, Tinay AHEl. Influence of traditional processing on minerals HCl-extractability of pearl millet (Pennisetum glaucum). Res J Agric Biol Sci. (2010) 6: 530–4.

Google Scholar

65. Adish AA, Esrey SA, Gyorkos TW, Jean-Baptiste J, Rojhani A. Effect of 610 consumption of food cooked in iron pots on fe status and growth of young children: a randomised trial. The Lancet. (1999) 353:712–six. doi: 10.1016/S0140-6736(98)04450-10

PubMed Abstract | CrossRef Full Text | Google Scholar

66. Geerlings PPD, Brabin BJ, Hart DJ, Fairweather-Tait SJ. Iron contents of malawian foods when prepared in fe cooking pots. Int J Vitam Nutr Res. (2004) 74:21–6. doi: 10.1024/0300-9831.74.i.21

PubMed Abstract | CrossRef Full Text | Google Scholar

67. Harvey PWJ, Dexter PB, Darnton-hill I. The touch of consuming iron from non-food sources on fe condition in developing countries. Public Health Nutr. (2000) 3:375–383. doi: x.1017/S1368980000000434

PubMed Abstruse | CrossRef Total Text | Google Scholar

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