Iron (Heme)

Animal models have suggested the carcinogenic effect of iron due to its oxidative potential. The lung is particularly vulnerable to oxidative stress. However, epidemiological studies investigating the association between dietary iron and the risk of lung cancer have reported inconclusive results. In this systematic review and meta-analysis, we aimed to clarify this association. Methods: We searched PubMed, Web of Science, Scopus and Google scholar for eligible articles published through May 2023 reporting the Relative Risk (RR), Hazard Ratio (HR) or Odds Ratio (OR) with 95% confidence interval (95% CI). Case-control and cohort studies that examined the relationship between dietary iron and lung cancer risk were included and review and meta-analyses articles, experimental studies, abstracts, letters to editor and studies with insufficient data were excluded. Finally, three case-control studies and 6 cohort studies were included. Random effect models were used to calculate the pooled results. Results: Nine studies (cases n=21,943, participants n=1,542,993) were included. There were no significant associations between the highest dietary total iron (heme and non-heme) (RR: 1.09, 95% CI: 0.78 to 1.51) or heme iron (RR: 1.01, 95% CI: 0.73 to 1.38) intake compared to the lowest intake with lung cancer risk. Null-associations were also observed in the subgroup analysis based on smoking status and lung cancer histology. However, in the subgroup of women (cases n=5074), heme iron was associated with a 14% increase in the risk of lung cancer (RR: 1.14, 95% CI: 1.01 to 1.29). Conclusions: The current results demonstrated that there is no significant relationship between dietary iron intake and the risk of lung cancer. However, a positive association was observed between dietary heme iron and the risk of lung cancer in women, which may require further investigation.

BACKGROUND: The role of iron biomarkers and iron intake in the susceptibility to lung cancer is unclear. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the relationship between iron levels in the body or iron intake and the risk of lung cancer. METHOD: This review is registered with PROSPERO (number CRD 42020199776). PubMed, Web of Science, Scopus, Embase and Cochrane were used to search for studies assessing the relationship between iron and lung cancer, up to July 15, 2021. Qualitative and quantitative analysis was carried out to determine if there was a correlation between iron biomarkers/intakes and the risk of lung cancer. RESULT: Twenty articles were included. Pooled analyses demonstrated that serum ferritin concentrations and transferrin saturation (TSAT) were significantly higher in patients with lung cancer than in healthy controls (ferritin: standardized mean differences [SMD], 0.235, 95% confidence interval [CI], 0.129, 0.341, I2 = 32.1 %; TSAT: SMD, 0.07, 95 % CI, 0.018, 0.121, I2 = 0 %). In contrast, serum transferrin concentrations were significantly lower in patients with lung cancer than in healthy controls (SMD, -0.591, 95 % CI, -1.18, -0.003, I2 = 87.7 %). No significant effects of serum iron, lung tissue iron, bronchoalveolar lavage fluid (BALF) ferritin, or iron intake (total iron, dietary iron, heme iron, or non-heme iron) were found on lung cancer incidence. CONCLUSION: Among the different iron biomarkers analyzed, a trend in association was only detected with serum ferritin, TSAT and transferrin concentration and no associations were found between iron intakes and the risk of lung cancer. However, more prospective studies are needed to strengthen the current evidence.

BACKGROUND AND OBJECTIVES: Many studies have investigated the association between dietary iron intake and death due to cardiovascular disease (CVD), but the results were inconsistent. We performed a dose-response meta- analysis to quantitatively assess the risk of CVD mortality with dietary intake of iron (total iron, heme iron, and non-heme iron). METHODS AND STUDY DESIGN: PubMed and Embase databases were searched for articles published up to February 21, 2019. Prospective cohort studies were included if reporting relative risks (RRs) and 95% confidence intervals (CIs) for risk of CVD mortality associated with dietary iron intake. Restricted cubic splines were used to model the dose-response association. RESULTS: We included eight articles (19 studies including 720,427 participants [46,045 deaths due to CVD]) in the meta-analysis. When comparing the highest versus lowest level of dietary heme iron intake, the pooled RR for CVD mortality was 1.19 (95% CI, 1.01-1.39). With a 1-mg/day increase in dietary heme iron intake, the pooled RR for death due to CVD, stroke, coronary heart disease, and myocardial infarction were 1.25 (95% CI, 1.17-1.33), 1.17 (1.04-1.32), 1.25 (0.70-2.22), and 1.17 (0.55-2.50) respectively. The association between dietary iron intake and CVD mortality was linear (pnonlinearity> 0.05). CONCLUSIONS: Higher dietary intake of heme iron was associated with a greater risk of CVD mortality. Reducing consumption of heme iron may help to prevent premature death due to CVD.

Comment in Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1435. doi: 10.1158/1055-9965.EPI-14-0214. Iron has been suggested as a risk factor for different types of cancers mainly due to its prooxidant activity, which can lead to oxidative DNA damage. Furthermore, subjects with hemochromatosis or iron overload have been shown to have a higher risk of developing liver cancer. We have systematically reviewed 59 epidemiologic studies, published between 1995 and 2012, reporting information on total iron, dietary iron, heme iron, and biomarkers of iron status and cancer risk. Furthermore we conducted meta-analysis for colorectal [relative risk (RR), 1.08; 95% confidence interval (CI), 1.00-1.17], colon (RR = 1.12; 95% CI, 1.03-1.22), breast (RR = 1.03; 95% CI, 0.97-1.09), and lung cancer (RR = 1.12; 95% CI, 0.98-1.29), for an increase of 1 mg/day of heme iron intake. Globally, on the basis of the systematic review and the meta-analysis results, a higher intake of heme iron has shown a tendency toward a positive association with cancer risk. Evidence regarding high levels of biomarkers of iron stores (mostly with serum ferritin) suggests a negative effect toward cancer risk. More prospective studies combining research on dietary iron intake, iron biomarkers, genetic susceptibility, and other relevant factors need to be conducted to clarify these findings and better understand the role of iron in cancer development.

BACKGROUND: Although recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. OBJECTIVES: This study evaluated the effects of 500 mg daily calcium supplementation as compared to 1500 mg calcium supplementation during pregnancy on maternal anemia and iron indices. METHODS: We conducted two individually randomized, noninferiority trials in India and Tanzania (N = 11,000 each) comparing daily 500 to 1500 mg calcium supplementation during pregnancy. All participants received standard iron and folic acid (IFA) (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 wk of gestation, whereas a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared with 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8953 and 1336 participants in India, respectively. In Tanzania, 8496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSIONS: Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of coadministering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. This trial was registered at ClinicalTr

BACKGROUND: Iron deficiency (ID) is associated with decreased appetite and altered mood, which can contribute to feelings of early satiety and reduced overall well-being. Few studies have examined differences in appetite, satiety, and mood between meals containing animal meat and plant-based meat, or whether improving iron status in those with ID improves these outcomes. OBJECTIVES: The objective of this study was to determine appetite, satiety, and mood after consumption of a meal containing animal meat or plant-based meat at baseline and after consuming the meal with an iron supplement once a day for 8 weeks in women of reproductive age (WRA) with ID. METHODS: In this randomized, double-blind, parallel-arm study, 52 nonpregnant WRA (24 ± 7 y; BMI: 22.9 ± 3.0 kg/m2) with ID (serum ferritin: 13.7 ± 6.0 μg/L) consumed an iron supplement with a lunch meal containing either 4 oz. of beef (Animal) or Beyond Meat (Plant) once a day for 8 weeks. Meals were calorically matched but differed in macro- and micronutrient composition due to the inherent differences between protein sources. For this secondary analysis, at baseline and endpoint, fasted participants consumed a standardized lunch meal containing beef or plant-based meat and rated appetite (fullness, hunger, desire to eat, and prospective consumption) using 100 mm visual analog scales. A composite satiety score was calculated. The Profile of Mood States questionnaire was assessed at baseline and endpoint. RESULTS: Indicators of iron status and anemia improved after 8 weeks (P < 0.05 for all) but did not differ between Animal and Plant. Hunger and desire to eat decreased, and fullness and composite satiety score increased after the meal (P-time < 0.0001 for all). Measures of appetite, satiety, and mood did not differ between Plant and Animal at baseline or endpoint. Changes in transferrin saturation (r = 0.4, P < 0.01) and hemoglobin (r = 0.3, P = 0.04) and hematocrit (r = 0.3, P = 0.03) were positively associated with changes in prospective food consumption, and changes in transferrin saturation were negatively associated with satiety (r = -0.3, P = 0.02). Changes in transferrin saturation (r = 0.3, P = 0.03) an

BACKGROUND: Anemia is a global health concern. It is disproportionately prevalent among pregnant women in low-resource regions, where iron deficiency is the leading cause. Given the multifactorial nature of anemia, a range of nutritional interventions is recommended. However, effective implementation is often hindered by limited health care access, poor adherence to supplementation, and gaps in nutrition knowledge and counseling. To address these challenges and optimize hemoglobin (Hb) levels among pregnant women, mobile health (mHealth)-based nutritional interventions offer a promising alternative. OBJECTIVE: The aim of the study is to review available evidence on the effectiveness of mHealth-based nutritional interventions on iron status (Hb and/or serum ferritin concentration) among pregnant women. METHODS: Searches were conducted in Embase, CINAHL, Cochrane Library, PubMed, Web of Science, and Scopus, and supplemented by snowballing to identify additional relevant studies from citation lists. The key search strings comprised 4 concepts: "mobile health," "nutritional intervention," "Hb, anemia or iron deficiency anemia," and "pregnant women." Predefined inclusion and exclusion criteria were applied during screening. The methodological quality of included studies was assessed using the Risk of Bias 2 tool. The primary end point was the change in mean Hb concentration or serum ferritin level. Effect sizes (ESs) were calculated as standardized mean differences, including Cohen d and Hedges g. RESULTS: Of the 14,284 studies identified, only 11 randomized controlled trials were included. These studies used various modes of delivery, including mobile phone calls (n=1), SMS text messaging (n=3), and mobile apps (n=4), with some using more than 2 modes (n=3). The effect of mHealth-based nutritional interventions on iron status varied significantly. In total, 4 studies demonstrated a large ES (>0.8), with 3 relying on WhatsApp Messenger as an mHealth delivery mode. Approximately 82% (9/11) of the included studies reported a positive effect (P values ranging from <.001 to .047) of the intervention on Hb level, whereas 2 studies reported no statistically significant ass

BACKGROUND: Gestational weight gain (GWG) during pregnancy is a critical factor that affects maternal and child health outcomes. The considerable burden of inadequate GWG and the rising tide of excessive GWG are overlooked challenges in low and middle-income countries (LMICs). METHODS: This systematic review assessed the impact of antenatal interventions on GWG in LMICs. Randomised controlled trials (RCTs) on antenatal interventions on GWG in LMICs were included. These interventions included educational, behavioural, nutritional supplementation and pharmacological therapies. A systematic literature search was conducted using PubMed, Embase, Web of Science, CINAHL and the Cochrane Library from the start of each database through September 2025. RESULTS: Out of the 33 642 unique articles identified, 70 articles were included in our systematic review, with 59 individual RCTs and 11 cluster RCTs. Nutritional interventions (31 studies) included food and micronutrient supplementations. Micronutrient supplementation such as multiple micronutrient supplementations was found to reduce the risk of severely inadequate or inadequate GWG among pregnant women compared to iron only or iron and folic acid supplementation (Grading of Recommendations Assessment, Development and Evaluation [GRADE]: moderate certainty). Food supplementation showed mixed results, although most trials demonstrated higher mean GWG among undernourished pregnant women and a greater likelihood of achieving Institute of Medicine-recommended ranges (GRADE: moderate certainty). Behavioural (counselling/education) interventions (20 studies) were associated with significant reductions in excessive GWG among pregnant women with overweight or obesity and improved adequacy of GWG (GRADE: moderate certainty). Physical activity (seven studies) was found to reduce the risk of excessive GWG (GRADE: moderate certainty). Combined dietary and physical activity interventions (six studies) were found to reduce the risk of excessive GWG among pregnant women (GRADE: low certainty). CONCLUSIONS: Well-structured antenatal interventions, initiated before 20 weeks of gestation and continuing beyond this period, tailored to loca

BACKGROUND: Prenatal multiple micronutrient supplementation (MMS) including iron, folic acid, and other essential micronutrients, has shown potential to improve birth outcomes in controlled studies. We did an effectiveness study in Ethiopia to determine the effect on mean birthweight of MMS provided as part of routine antenatal care, relative to iron-folic acid supplementation (IFA). METHODS: A pragmatic, two-arm, facility-based, cluster-randomised controlled trial was conducted across 42 districts in five regions of Ethiopia to determine the effect on birthweight of MMS relative to IFA. Districts were randomly assigned to either retain IFA as part of routine antenatal care or switch to MMS. Randomisation was stratified by region and done using a random number generator within statistical software. All live singleton births at participating health facilities were eligible for inclusion and birthweights were recorded. Additionally, data were collected on maternal receipt and utilisation of MMS or IFA. The primary outcome was birthweight, analysed in the intention-to-treat population. This completed trial is registered at ClinicalTrials.gov, NCT05708183. FINDINGS: Between Jan 1, 2023, and Dec 31, 2024, birthweights were recorded for 47 325 babies in the 21 IFA districts and 36 473 babies in the 21 MMS districts. Mean age of mothers was 26·2 years (SD 5·3) and median gestational age of babies at birth was 38 weeks (IQR 38-39). The effect of MMS on birthweight was a mean increase of 38 g (95% CI 20-55) in the MMS arm relative to the IFA arm after adjustment for time, geographical region stratification factor, gestational age, sex of baby, and parity. Among women who reported taking at least 90 tablets of their assigned supplement, the increase in mean birthweight in the MMS arm relative to the IFA arm was 58 g (38-79). Stillbirth risk was 7·5 per 1000 births in the IFA arm and 6·9 per 1000 births in the MMS arm. INTERPRETATION: The findings of this trial are consistent with those from efficacy trials in other settings, indicating that the transition from IFA to MMS as part of routine antenatal care in Ethiopia could lead to a small but clear improvement in birthweig

BACKGROUND: Anemia affects more than two-thirds of children aged <5 y in India, despite biweekly iron folic acid (IFA) supplementation under the Anemia Mukt Bharat national program. Multiple micronutrient (MMN) deficiencies may also contribute to the presence of anemia, but the incremental benefit of MMN supplementation in addition to IFA remains unclear. OBJECTIVES: We aimed to compare the efficacy of biweekly preventive supplementation with MMNs plus IFA compared with IFA alone on hemoglobin concentrations and prevalence of anemia in children aged 6-59 mo. METHODS: In this individually randomized, open-label trial, eligible children received biweekly supplementation with either MMN plus IFA (intervention) or IFA alone (control) for 100 doses over 50 wk. Primary outcomes were mean hemoglobin concentration and anemia prevalence. Secondary outcomes included serum ferritin, soluble transferrin receptor, vitamin B12, folate, and zinc. RESULTS: Among 1300 children enrolled (648 intervention and 652 control), supplementation compliance exceeded 75%. At the endline, the mean hemoglobin was slightly higher in the intervention group [adjusted mean difference, 0.12 g/dL; 95% confidence interval (CI): 0.00, 0.25]. The prevalence of anemia was 17.6% in the intervention group and 24.0% in the control group (adjusted relative risk, 0.72; 95% CI: 0.58, 0.90). No significant differences were observed in serum biomarkers of iron status or other micronutrients. CONCLUSIONS: Biweekly supplementation with MMN plus IFA resulted in a modest increase in hemoglobin concentrations and a relative reduction in anemia prevalence compared with IFA alone, particularly in older children. Lack of improvement in biochemical markers and a small rise in hemoglobin concentrations suggest that a reduction in the prevalence of anemia may be driven by shifts near diagnostic thresholds, rather than meaningful physiological benefits. MMN adds minimal value where IFA adherence is already high. The study was registered at Clinical Trial Registry of India as #CTRI/2020/10/028299 (https://ctri.nic.in/Clinicaltrials/login.php).

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition that affects attention, impulse control, and the ability to remain still. These challenges can make it harder for individuals with ADHD to succeed at school, work, and in social situations. Stimulant medications, such as methylphenidate and amphetamines, are commonly used as first-line treatments and are effective at reducing symptoms. However, their use can be limited by side effects, such as insomnia, appetite loss, cardiovascular risks, potential for misuse, and variability in individual response. Since current treatments have drawbacks, many people are exploring nonstimulant options, such as behavioral therapy, dietary changes, and neurofeedback. These approaches may be safer and easier to maintain, but research on their effectiveness remains uncertain. This systematic review and meta-analysis aim to compare the effectiveness of pharmacological and nonpharmacological therapies for ADHD. METHOD: We systematically searched PubMed, PsycINFO, Cochrane Library, ClinicalTrials.gov, and IEEE Xplore for randomized controlled trials (2008-2023) evaluating pharmacological (e.g., stimulant medications), non-pharmacological (e.g., behavioral therapy, cognitive training), or combined interventions in children and adolescents with ADHD. The search yielded 318 records. After screening titles and abstracts, 249 were excluded. Sixty-nine full-text articles were assessed, and 18 RCTs met the inclusion criteria for analysis. Primary outcomes were reductions in ADHD symptoms measured by standardized rating scales; secondary outcomes included academic performance, social functioning, and clinical global impression. RESULTS: Eighteen RCTs were pooled. ADHD symptoms were consistently reduced with stimulant medications (methylphenidate and amphetamines), although effects on academic performance were modest. Non-stimulants, such as viloxazine and guanfacine, showed significant improvements on ADHD-RS scores, but these improvements were only clinically modest. In contrast, some nutritional supplements, particularly iron and omega-3 fatty acids, showed more pronounced benefits in sympt

BACKGROUND: Maternal periconceptional nutrition is important for birth outcomes, but few studies examine long-term effects on offspring growth and development. OBJECTIVES: We assessed the impact of weekly preconception multiple micronutrients (MM) or iron and folic acid (IFA) supplements compared to folic acid (FA) alone, on cognitive function and nutritional status at 10-11 y. We also examined associations with early-life biological and socioenvironmental factors. METHODS: We conducted a follow-up study of 1599 children from a preconception randomized trial in Vietnam, in which females received weekly FA, IFA, or MM before conception and daily IFA during pregnancy. We assessed cognitive function, academic achievement, and nutritional status at ages 10-11 y. Early biological factors included maternal nutritional status, birth characteristics, and postnatal linear growth; socioenvironmental variables were maternal schooling, ethnicity, depression, infant feeding, socioeconomic status (SES), and home environment. Analyses used intention-to-treat and per protocol comparisons with inverse-probability-of-censoring weights to account for loss to follow-up. RESULTS: Offspring in the MM and IFA groups had higher perceptual reasoning scores than the FA group {mean difference [95% confidence interval (CI): MM: 1.68 (0.01, 3.35); IFA: 2.04 (0.33, 3.74)]}. The IFA groups also had higher reading scores [0.78 (0.11, 1.44)] and lower anemia prevalence [-4.26 (-7.60, -0.91)]. No differences were observed in full-scale intelligence quotient (FSIQ) or anthropometric measures. Maternal underweight was negatively associated with FSIQ [β (95% CI): -1.62 (-3.06, -0.18)] and reading scores [-0.59 (-1.12, -0.06)] whereas postnatal linear growth was positively associated with FSIQ [1.67 (0.91, 2.43)], mathematics [0.36 (0.12, 0.61)], and reading scores [0.47 (0.21, 0.74)]. Maternal schooling, home environment, SES, were also linked to improved cognitive and academic outcomes [β range: 0.64 (0.01, 1.27) to 8.89 (5.20, 12.58)], and exclusive breastfeeding was linked with higher mathematics scores [0.73 (0.27, 1.19)]. CONCLUSIONS: Preconception MM and IFA supplementation improved certain a

BACKGROUND: Caloric restriction (CR) is a promising nutritional intervention for improving metabolic and age-related health outcomes, but its long-term effects on hematologic health remain unclear. Clarifying how prolonged CR affects anemia risk and iron status is essential for evaluating its long-term safety and clinical relevance. OBJECTIVES: To determine the effects of a 2-y CR intervention on markers of anemia, iron status, and hepcidin in females and males enrolled in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 2 trial. METHODS: Participants in CALERIE Phase 2 (n = 220) were randomly assigned to 25% CR or ad libitum (AL) control. AL continued their habitual diet, whereas CR received an intensive intervention to promote CR over 2 y. All participants received a multivitamin/mineral supplement containing 18 mg iron. Fasted blood was collected at baseline (BL) and 12 (M12) and 24 (M24) mo and indicators of iron status (ferritin, soluble transferrin receptor, and serum iron), anemia (hemoglobin and hematocrit), and regulators of iron status (hepcidin, C-reactive protein, and IL-6) were measured. Six-day diet diaries were collected twice at BL and once each at M12 and M24. An anemia surveillance protocol monitored hemoglobin, hematocrit, red blood cell (RBC) count, and serum iron throughout the intervention, with medical evaluation and temporary/permanent CR discontinuation as needed. Linear mixed-effects models were used to evaluate the effect of treatment (CR compared with AL), time (BL, M12, and M24), and their interaction (treatment × time). RESULTS: Participants (n = 218) were mostly female (70%) with an mean age (±SD) of 38.1 ± 7.2 y and a mean BMI of 25.2 ± 1.7 kg/m2. At baseline, ferritin (105.5 ± 126.9 μg/L), hepcidin (8.6 ± 5.8 ng/mL), and dietary iron intake (16.1 ± 5.5 mg/d) were similar between groups (P > 0.05). There were no group × time interactions for markers of anemia, indicators of iron status, or hepcidin (P > 0.05). Despite the anemia surveillance protocol, anemia prevalence remained >5% in both groups across all timepoints. Low RBC count was the most common trigger, and participants who tri

Oxidative stress (OS) arises from an imbalance between antioxidant defenses and the generation of reactive oxygen species (ROS), both of which are influenced by the levels and composition of trace elements. The Micronutrients for ADHD in Youth randomized controlled trial demonstrated behavioral improvements following 8 weeks of multinutrient supplementation in 54% of children compared to 18% on placebo. This secondary analysis examined the relationship between plasma minerals and OS-related parameters [biological antioxidant potential (BAP), glutathione peroxidase (GPx), glutathione reductase (GR), and reactive oxygen metabolites (ROM)] in 71 children (44 multinutrient, 27 placebo; median age 10.4 years). Correlation analysis revealed that selenium and zinc improved antioxidant response measured as GPx change in both treatment groups (r = 0.26, p = 0.03) and BAP in multinutrient group (r = 0.37, p = 0.01), respectively, while chromium change was inversely related to BAP (r=-0.41, p = 0.005) in the multinutrient group. BAP change was moderated by baseline selenium (β=-9.45, p = 0.006), zinc (β=-2.13, p < 0.001), and chromium (β = 68.9, p = 0.02), where children in the multinutrient group with low selenium, low zinc, and high chromium at baseline experienced BAP increases. Selenium also exhibited pro-oxidant effects: ROM change correlated positively with change in selenium in multinutrient group only (r = 0.34, p = 0.03). Baseline copper predicted ROM change (β = 0.213, p < 0.001), and ROM change correlated positively with changes in copper in both groups (r = 0.51, p < 0.001) and negatively with Mn (r=-0.24, p = 0.05), while iron did not moderate OS. Multinutrient supplementation may enhance antioxidant defenses in children who had low plasma zinc and selenium, while potential pro-oxidant effects in those with higher selenium and chromium warrant further investigation. Clinical Trial Registry number for MADDY RCT: NCT03252522. © 2026. The Author(s).

Celiac disease (CeD) is a gluten-induced immune-mediated enteropathy that preferentially involves the proximal duodenum. Consequently, iron deficiency is common in CeD, impacting at least 10% of newly diagnosed individuals. In this narrative review, we aim to investigate the mechanisms, prevalence, treatment, and monitoring of iron deficiency and the impacts of a gluten-free diet (GFD) on iron deficiency in individuals with CeD. We will also review the role of and approach to iron supplementation in this population. Specifically, we will explore whether mucosal healing on a GFD is sufficient for the management of iron deficiency amongst individuals with CeD.

BACKGROUND: Malaria is an infectious disease transmitted by female Anopheles mosquitoes, with ongoing transmission in over 80 countries. The malaria parasite requires folate for survival and growth; antifolate antimalarial medications used for prevention and treatment target enzymes in folate metabolism as their mechanism of action. Periconceptional folic acid (synthetic form of folate) supplementation (400 μg/day) is the standard of care for neural tube defect prevention. Concerns have been raised about the potential effects of folic acid (including above the tolerable upper intake level (UL) >1.0 mg/day) in the context of malaria prevention and treatment, including the efficacy of antimalarial medications. Examining the potential impact of folic acid on malaria risk and severity amongst people taking antifolate antimalarial medications may inform public health programmes in malaria-endemic areas. OBJECTIVES: To examine the effects of folic acid supplementation on the risk and severity of malaria infection amongst people taking antifolate antimalarials and living in areas with malaria endemicity. PREVENTION: Amongst uninfected people taking antifolate antimalarial medications for malaria prevention, does folic acid supplementation increase susceptibility or severity of malaria infection? TREATMENT: Amongst people with malaria infection who are being treated with antifolate antimalarial drugs, does folic acid supplementation reduce parasite clearance or increase the risk of treatment failure? SEARCH METHODS: We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, Scopus, and trial registries (September 13, 2024), grey literature, and reference searches to identify additional studies. SELECTION CRITERIA: Randomised trials evaluating the effects of folic acid supplementation (alone or in combination with iron or other vitamins and minerals) amongst individuals taking antifolate antimalarial medications in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: Primary outcomes included uncomplicated malaria or severe malaria, parasite clearance, and treatment failure. Cochrane RoB 2 was used to evaluate the risk of bias. Certainty of evidence was assessed u

BACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four

BACKGROUND & AIMS: Iron deficiency (ID) is a global health condition that predominately affects women. Although oral iron supplementation is an effective treatment strategy for this issue, gastrointestinal complaints are common, and if persistent, may lead to poor compliance. The efficacy of different iron formulations which claim to improve tolerance is unclear. This study assessed the efficacy and tolerability of ferrous sulphate (FS) and iron (III)-hydroxide polymaltose complex (IPC) supplementation in three different cohorts of women.. METHODS: This study implemented a 12-week, single-blind, randomized controlled trial. Eligible participants had a serum ferritin concentration of <50 μg/L and met specific inclusion criteria to be enrolled to either the athlete, pre-menopausal or post-menopausal groups. Participants were randomized to receive FS (equivalent to 105 mg elemental iron) plus sodium ascorbate or IPC (equivalent to 100 mg elemental iron) daily. Venous blood samples were collected at baseline, 4-, 8- and 12-weeks of supplementation. A daily questionnaire was completed throughout the study period, documenting supplement tolerance (number and severity of symptoms), exercise load, menstrual characteristics, and supplement compliance. RESULTS: Fifty-seven participants completed the intervention with a compliance rate of 94.9 % [range: 74.8-100 %]. A significant interaction between supplement and time was evident for ferritin (p < 0.001), where FS increased after 12 weeks (+109 %; p < 0.001) but no change was evident in IPC (+7 %; p = 0.727). No differences were detected between cohorts (p > 0.05). The IPC group had a lower symptom rate compared to FS (28 % vs. 33 %; p < 0.001).. CONCLUSIONS: FS was superior in repleting ferritin concentrations after 12 weeks compared with IPC; however, FS also resulted in a greater number and severity of GI symptoms than IPC. Our data shows FS is the superior iron formulation for ID treatment, however future research should continue to address how to improve FS tolerance.. This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview as ACTRN12623000529640.

BACKGROUND: Despite substantial increases in access to schooling and to the internet, health information and knowledge remains limited among women of reproductive health in many low- and middle-income countries. Given the near universal cell-phone coverage in low- and middle-income countries, call-in services offer an interesting new platform to provide high quality information to targeted populations. In this paper, we assessed the impact of the Viamo 3-2-1 call-in platform on health knowledge and behavior among women of reproductive age in Uganda. METHODS: We conducted a 2-arm open label randomized controlled trial targeting 6000 women, ages 18-49 years, with access to a simple feature Airtel cell phone in Uganda. Fifty enumeration areas were randomly selected in Kampala, Madi-Okollo, Rwampara and Katakwi districts for a total of 200 enumeration areas. Consenting women were asked to complete a baseline and endline survey implemented by trained interviewers using tablets through home visits. After completion of baseline, women were randomized with equal probability to treatment and control using a tablet-generated random number draw. Study staff introduced treated women to the call-in service and encouraged its use through various incentives and promotional messages. Primary outcomes were sexual and reproductive health knowledge scores as well as iron supplementation in pregnancy. Secondary outcomes included self-reported use of contraception, healthy diets, birth spacing and birth outcomes as well as hemoglobin levels and BMI. Linear regression models were used to estimate mean differences in outcomes between treatment and control. Standard errors were corrected for the cluster-based sampling of women. RESULTS: A total of 6,011 women were enrolled into the study between December 6, 2022 and February 11, 2023; 3,052 were assigned to treatment, 2,959 used as controls. Endline data was collected between May 8, 2024 and August 4, 2024. Overall follow-up rates were 92% in both the treatment and the control group. Treatment increased average sexual and reproductive health knowledge by 0.07 standard deviations (95% CI [0.01, 0.11], p-value = 0.02) and increased the l