Perspectives on Iron Deficiency as a Cause of Human Disease in Global Public Health.

Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines.

Vitamin D3 Bioaccessibility from Supplements and Foods-Gastric pH Effect Using a Static In Vitro Gastrointestinal Model.

Vitamin D3 deficiency is a global phenomenon, which can be managed with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors such as matrix composition and interactions throughout the gastrointestinal (GI) tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, as well as the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the initial vitamin D3 content in the supplements and foods, as well as after each digestion stage. The results indicate that the foods exhibited higher bioaccessibility indices compared to the supplements and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between an increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to a low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e., gastric pH = 1) enhance the vitamin's bioaccessibility.

Association of Fortification with Human Milk versus Bovine Milk-Based Fortifiers on Short-Term Outcomes in Preterm Infants-A Meta-Analysis.

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Market assessment of fortified parboiled rice in Burkina Faso.

Micronutrient deficiency remains a daunting issue in many parts of the world. Effective interventions are needed to deal with the problem, which should consider production and consumption traditions and trends to improve their success. Parboil rice is a growing staple in Burkina Faso, where micronutrient deficiency remains high. This paper assesses the market feasibility of fortified rice through parboiling using a limited-water soaking method. Our findings suggest that consumers are willing to pay a premium for fortified rice versus conventional parboiled rice after they are informed about the importance of the problem and the potential benefits of fortified rice. A stylized cost analysis also reveals that the cost of producing fortified rice using a limited-water soaking method could exceed the premiums consumers are willing to pay, and therefore that public intervention may be needed to improve the odds of adoption by consumers. The findings have implication beyond Burkina Faso, and could guide market development in other regions where production and consumption of parboiled rice is well established.

The Use of a Novel Donkey Milk-Derived Human Milk Fortified in the Neonatal Period Had No Effect on the Frequency of Allergic Manifestations During the First Years of Life: The "Fortilat Trial" Follow-Up.

Background: Since human milk contents does not meet the high need of very low birth weight infants, fortification of breast milk is a standard practice for this population. As donkey milk has been long considered for children allergic to cow's milk proteins due to its low allergic properties, a new donkey milk-derived fortifier (DF) has been recently evaluated as a valid alternative to bovine milk-derived fortifier (BF). It seems to improve feeding tolerance when compared with standard BF, with similar neurodevelopmental and auxological outcome at 18 months of age. The aim of this study is to evaluate the development of allergic manifestations occurring in the population of the "Fortilat Trial" at 6-8 years of age. Methods: Allergic manifestations were assessed by an ad hoc questionnaire administered to families. The occurrence of asthma, allergic rhinitis and oculorhinitis, rashes and atopic dermatitis, food allergies, accesses to an emergency department for allergic reactions, and the need of antihistamine have been investigated. Results: In total, 113 infants were enrolled in the study (BF arm: n = 60, DF arm: n = 53). No difference in risk was observed between the two groups for all the considered outcomes. In conclusion, our data suggest that DF does not impact the development of allergic manifestations in the first years of life. Clinical Trial Registration number: ISRCT N70022881.

Folic Acid-Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India: A Nonrandomized Controlled Trial.

Importance: India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. Objective: To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. Design, Setting, and Participants: This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Intervention: Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Main Outcomes and Measures: Change in median serum folate levels between baseline and study end point as the primary outcome of the study. Results: A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Conclusions and Relevance: Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT06174883.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Older adults' acceptability of and preferences for food-based protein fortification in the UK, France and Norway.

Research suggests that as we age, protein intake, recognised as vital for combating negative health outcomes, consistently falls below recommendations in older adults. Decreased food intake, combined with age-related eating complications is a major determinant of this protein undernutrition. If nutritional interventions are to be effective and sustainable, they must enable eating pleasure, cater for personal preferences and be adaptable to different eating patterns. As such, we aimed to identify successful strategies for at-home protein-fortification to empower older adults to take a personalised approach to their nutrition, without requiring a large behavioural change. To explore healthy older adults' (age 70+) acceptability and preferences for at-home protein fortification, European project Fortiphy led discussions with older adults (n = 37) and caregivers of older adults (n = 15) to develop high-protein recipes, which were then utilised in a home-use trial with healthy older adults (n = 158). Each fortified recipe was paired with a questionnaire to rate the ease of preparation and liking, and an end-of-study questionnaire was provided to capture overall opinions and preferences. The uniqueness of this study is that the protein fortified recipes were prepared and tested by older adults themselves, in their own homes. Findings showed that older adults were unaware of the importance of protein in ageing and did not have a desire to fortify their foods at present. Yet, they were positive regarding the concept and highlighted the importance of taste, familiar ingredients, and preferred preparation methods. Cultural preferences across countries were identified as having the most influence on the liking of fortified meals. This study also indicated a need for increased awareness of protein requirements to influence the motivation to use fortification.

Micronutrient deficiency and supplements in schoolchildren and teenagers.

PURPOSE OF REVIEW: The essential micronutrients are corner stones in the functional and physical development. Early deficiency has life-long consequences. While awareness about iron deficiency is relatively high, it remains lower for other micronutrients. This review aims at reporting on recent data and attracting attention to the high prevalence of micronutrient deficiencies in school-age and adolescent individuals. RECENT FINDINGS: Iron deficiency anaemia remains highly prevalent worldwide and the most frequent deficiency but can be corrected with simple tools ranging from food fortification, nutritional intervention, and to supplements. The link between micronutrient (MN) deficiency and neurobehavioral disorders is increasingly established and is worrying even in Western countries. Paediatric individuals are prone to imbalanced diets and picky eating behaviour, and their diets may then become incomplete: the highest risk for deficiency is observed for iron, zinc and vitamin D. SUMMARY: There is not much new information, but rather confirmation of the importance of health policies. Well conducted randomized controlled trials confirm that deficiencies can be corrected efficiently including with food fortification, and result in clinical benefits. Individual complementation should be considered in children and adolescents with proven deficiency.

Vitamin D fortification of foods - sensory, acceptability, cost, and public acceptance considerations.

In terms of vitamin D food fortification, there are a number of important considerations in relation to selection of the food vehicle and fortificant. While there has been much research focus on the ability of fortified foods to improve vitamin D status, other considerations, such as sensory properties and acceptability, cost, and public attitudes around vitamin D-fortified foods, have received less attention. Thus, the present narrative review aimed to summarize the existing knowledge around these important considerations. In summary, its findings suggest that: i) vitamin D addition to various food vehicles, at levels consistent with the supply of part or all the recommended intake, does not alter their sensory characteristics or overall acceptability; ii) overall, vitamin D fortification of foods is relatively cost-effective, despite the fact that some attitudinal studies highlighted participant concerns about the potential cost/expense of vitamin D-fortified foods; iii) evidence from various attitudinal studies suggest a high level of acceptance and/or purchase intention (i.e., extent to which customers are willing and inclined to buy) of vitamin D-fortified food products by the general public; and iv) there have been repeated calls for vitamin D public health educational/information campaigns to help educate consumers about the health risks associated with vitamin D deficiency and nutritional benefits associated with consumption of vitamin D-fortified foods. Such campaigns could positively mediate attitudes and acceptance of vitamin D-fortified foods amongst the public, and could also help address misconceptions and allay fears around vitamin D for concerned individuals. Lastly, the findings of the present review also highlight the existence of between-country differences, even within Europe, in relation to attitudes and purchase intention of vitamin D-fortified foods and the perceived appropriateness of certain food vehicles for vitamin D fortification, as well as the best mix of communication channels for a vitamin D public health educational/information campaign.

Maize gets an iron boost: Biofortification breakthrough holds promise to combat iron deficiency.

This commentary describes recent research discovering that the NAC transcription factor gene ZmNAC78 controls iron intake in maize and its implications for biofortification of this important crop. Using ZmNAC78, iron levels in maize can be more than doubled compared with current varieties.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Preventing and Controlling Zinc Deficiency Across the Life Course: A Call to Action.

Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is, thus, vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related noncommunicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zinc's role in health, the impact of the changing climate and global context on zinc intake, novel functional biomarkers showing promise for monitoring population-level interventions, and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combating global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions, including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent.

Curds in the way: A milk curd obstruction review and normal sonographic bowel appearances using a novel scoring system in neonates on fortified breast milk feeds.

INTRODUCTION: Fortified expressed breast milk (FEBM) is a standard of care for premature and low birth weight neonates, but comes with an elevated risk of a rare but re-emergent pathology called milk curd obstruction (MCO). Little is known about normal sonographic appearances of bowel contents in this feeding setting, making the recognition of abnormalities difficult. Thus, we aimed to describe appearances that may be considered typical pre- and post-fortifier inclusion. METHODS: Ten neonates of <32 weeks' gestation or a birth weight of <1,800 g recruited from Auckland City Hospital Neonatal Intensive Care between 1/5/2019 and 10/9/2019 received bowel ultrasounds within 24 h before and 10-14 days after starting FEBM. Bowel contents in six abdominal regions were assigned scores of 1-6 based on increasing solidification. RESULTS: Lower gestational age was correlated with more solid contents on the pre-fortifier ultrasound (P = 0.02). Fortifier was significantly associated with increasing solidity, particularly in the left abdomen (P < 0.001). The left lower quadrant and rectum accounted for much of this change (P = 0.012 and P = 0.002). One subject who subsequently developed a clinical picture consistent with early MCO had uniquely demonstrated non-rectal solid contents (score 6). The interobserver kappa score for two assessors was 0.91 (95% CI 0.94-0.99) on still images. CONCLUSION: This small cohort demonstrated increasing bowel content solidification after breast milk fortification using a novel ultrasound scoring system with good interobserver agreement. Non-rectal solid contents (score 6) appeared atypical. Ultrasound shows promise for its non-irradiating diagnostic utility in the setting of early milk curd disease evaluation of the premature neonate.

Biofortification's contribution to mitigating micronutrient deficiencies.

Biofortification was first proposed in the early 1990s as a low-cost, sustainable strategy to enhance the mineral and vitamin contents of staple food crops to address micronutrient malnutrition. Since then, the concept and remit of biofortification has burgeoned beyond staples and solutions for low- and middle-income economies. Here we discuss what biofortification has achieved in its original manifestation and the main factors limiting the ability of biofortified crops to improve micronutrient status. We highlight the case for biofortified crops with key micronutrients, such as provitamin D3/vitamin D3, vitamin B12 and iron, for recognition of new demographics of need. Finally, we examine where and how biofortification can be integrated into the global food system to help overcome hidden hunger, improve nutrition and achieve sustainable agriculture.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Relationship of dietary intake of food folate and synthetic folic acid intake from fortified foods with all-cause mortality in individuals with chronic kidney disease.

OBJECTIVE: To evaluate the association of the dietary intake of food folate (natural folate) and synthetic folic acid intake from fortified foods with the risk of all-cause mortality and end-stage kidney disease (ESKD) among the chronic kidney disease (CKD) population in regions with folic acid fortification. METHODS: 4028 individuals with established CKD in Chronic Renal Insufficiency Cohort (CRIC) were included. Diet was assessed using a validated diet history questionnaire at the baseline, year 2, and year 4, and nutrient intake, including food folate and folic acid from fortified foods, was estimated using the National Nutrient Database. The outcomes were all-cause mortality and ESKD. The results for all-cause mortality were further validated using the data from National Health and Nutrition Examination Surveys (NHANES). RESULTS: During a median follow-up of 11.1 years, 1155 deaths and 938 ESKD cases occurred. Compared with the first quartile of food folate intake, the third (HR: 0.74; 95% CI: 0.62, 0.90) and fourth (HR: 0.79; 95% CI: 0.63, 0.98) quartiles had a lower risk of all-cause mortality. Nevertheless, there was no significant association of synthetic folic acid intake from fortified foods with all-cause mortality. Similar results were observed for ESKD. Consistently, in NHANES, food folate intake and serum 5-methyltetrahydrofolate, but not folic acid intake, were inversely associated with all-cause mortality, while serum unmetabolized folic acid was positively associated with all-cause mortality in CKD participants. CONCLUSIONS: Higher intake of dietary natural folate, but not synthetic folic acid intake from fortified foods, was associated with lower risks of all-cause mortality and ESKD among CKD participants.

Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota.

Iron deficiency anemia (IDA) caused by micronutrient iron deficiency has attracted global attention due to its adverse health effects. The regulation of iron uptake and metabolism is finely controlled by various transporters and hormones in the body. Dietary iron intake and regulation are essential in maintaining human health and iron requirements. The review aims to investigate literature concerning dietary iron intake and systemic regulation. Besides, recent IDA treatment and dietary iron supplementation are discussed. Considering the importance of the gut microbiome, the interaction between bacteria and micronutrient iron in the gut is also a focus of this review. The iron absorption efficiency varies considerably according to iron type and dietary factors. Iron fortification remains the cost-effective strategy, although challenges exist in developing suitable iron fortificants and food vehicles regarding bioavailability and acceptability. Iron deficiency may alter the microbiome structure and promote the growth of pathogenic bacteria in the gut, affecting immune balance and human health.