The Journal of Nutrition

BackgroundWheat flour, maize flour and rice (i.e. grains) fortification with folic acid is an important folate dietary source globally. There are no systematic reviews or meta-analyses evaluating the effect of mandatory grain fortification on folate insufficiency (using serum/plasma folate and red blood cell (RBC) folate), RBC folate levels or folate deficiency using RBC folate. This study assessed the effectiveness of mandatory grain fortification with folic acid on serum/plasma folate and red blood cell (RBC) folate levels and the risk of folate deficiency and insufficiency based on these biomarkers. MethodsWe searched PubMed and Embase with assistance from a professional library informationist. We selected studies from countries with mandatory grain fortification that include folic acid in standards if they reported primary pre- and post-fortification data on folate status outcomes. We ran meta-analyses in R using random effects models with results expressed as meta-differences of means (MDM) or meta-prevalence ratios (mPR) for continuous and binary outcomes respectively. All meta-estimates were accompanied by 95% confidence intervals (CI). ResultsWe screened 4,311 documents, identifying 31 articles which reported folate status outcomes (22 reported mean serum/plasma or RBC folate, 18 reported prevalence of folate deficiency or insufficiency). About 19% of studies were conducted in low- or middle-income countries. Mandatory fortification improved folate status, albeit with considerable heterogeneity across studies (I2[≥]73%). For serum/plasma folate levels, the MDM across all studies was 15.0 nmol/L (95% CI: 9.4-20.5). For serum/plasma folate insufficiency and deficiency, the mPR (95% CI) estimates were 0.17 (0.08-0.37) and 0.08 (0.03-0.23), respectively. For red blood cell folate levels, the MDM was 329.4 nmol/L (95% CI 243.9-414.9). For RBC folate insufficiency and deficiency, mPRs (95% CIs) were 0.16 (0.08-0.30) and 0.05 (0.01-0.46), respectively. ConclusionsMandatory grain fortification with folic acid increases blood folate levels and decreases the risk of folate insufficiency and folate deficiency.

BackgroundPregnant women are advised to take folic acid supplements before conception and during the first three months of pregnancy. Many women continue folic acid supplementation throughout pregnancy, and concerns have been raised about associations between excess folic acid intake and adverse child health outcomes. Unmetabolized folic acid (UMFA) is found in serum at higher folic acid intakes and has been proposed as a biomarker for excess folic acid intake. ObjectiveTo determine if removing folic acid from prenatal multivitamin and mineral supplements after 12 weeks of pregnancy reduces concentrations of serum UMFA at 36 weeks gestation. DesignA double-blind, parallel-group, randomized controlled trial. Women with a singleton pregnancy 12-16-weeks gestation were randomly assigned to a multi-micronutrient supplement containing no folic acid (intervention) or 800 {micro}g folic acid/day (control) from enrolment until 36 weeks gestation. Maternal serum was analyzed for UMFA and secondary outcomes of red blood cell and serum folate at 36 weeks gestation. ResultsUMFA was detected in most of the 103 randomized women (86% >limit of detection). However, only 12% (n=11/90) of serum samples were above the limit of quantification (0.55 nmol/L), preventing analysis of UMFA concentrations. Fewer women had detectable UMFA in the no folic acid group compared to the 800 {micro}g folic acid group (72% [n=33/46] vs. 98% [n=43/44]; p = 0.001). Maternal serum and red blood cell folate concentrations were lower in the no folic acid intervention group compared to the control group (median 23.2 vs. 49.3 nmol/L, 1335 vs. 1914 nmol/L, respectively; p< 0.,001) and no woman was classified as folate deficient. ConclusionsRemoving folic acid from prenatal multivitamin and mineral supplements reduced the number of women with detectable UMFA at 36 weeks gestation, however, differences in UMFA concentration between treatment groups were not quantifiable.

BackgroundPoorly planned vegan diets may incur deficiencies in indispensable amino acids (IAAs) and certain micronutrients. Targeted dietary modifications are necessary to improve nutrient adequacy for optimal health. ObjectiveOptimisation modelling was applied to identify combinations of plant-based foods within an individuals existing diet to address protein and IAA shortfalls in a sample of New Zealand vegans grouped into three clusters with varied daily dietary patterns. MethodsShortfalls for protein and IAAs were calculated by comparing daily intakes to individual requirements. An energy-tailored optimisation using linear programming was used: diets with lower energy intake had foods added while those with excess energy had energy-dense and low-protein foods replaced with protein-rich alternatives. The modified diets had to 1) meet protein and IAA shortfalls, 2) respect serving size constraints for added foods, and 3) remain within individual energy boundaries while minimising the weight of food added. Post-optimisation analysis assessed changes in intake of protein, amino acids, dietary fibre and selected micronutrients with results compared across clusters. ResultsProtein and IAA shortfalls were more prevalent in cluster 1 (85% of daily diets) compared to clusters 2 (61.1%) and 3 (30.8%). Legumes and pulses contributed most to total protein and lysine with lower energy costs, while nuts and seeds contributed most to methionine and leucine, but with higher energy. Optimisation resolved shortfalls in 93.2% of the daily diets. The remaining 52 diets - mainly from clusters 1 and 2 - could not reach adequacy due to large protein and IAA deficits and limited energy capacity. Post-optimisation micronutrient analysis showed continued risks of shortfalls for calcium, vitamin B12 and iodine. ConclusionMathematical optimisation can enhance the protein adequacy of vegan diets while preserving individual acceptability. However, full nutritional adequacy remains challenging in energy-constrained diets with large nutrient deficits.

BackgroundEvidence-based practice (EBP) promotes shared decision-making between clinicians and patients and has been widely adopted by various health professions including nutrition & dietetics, medicine and nursing. ObjectiveTo determine evidence-based practice (EBP) competencies among nutrition professionals and students reported in the literature. DesignSystematic review. Data sourcesMedline, Embase, CINAHL, ERIC, CENTRAL, ProQuest Dissertations and Theses Global, BIOSIS Citation Index, and ClinicalTrials.gov up to March 2023. Eligibility criteria for study selectionEligible primary studies had to objectively or subjectively document the assessment of at least one of six predefined core EBP competencies, including formulating structured clinical questions, searching the literature for best evidence, and assessing studies for methodological quality, magnitude (size) of effects, certainty of evidence for effects, and determining the clinical applicability of study results based on patient values and preferences. Data extraction and synthesisTwo reviewers independently screened articles and extracted data, including the reporting quality for eligible studies. Results were not amenable to meta-analysis and were thus summarized for each EBP competency. ResultsWe identified 12 eligible cross-sectional survey studies, comprised of 1065 participants, primarily registered dietitians, across six countries, with the majority assessed in the United States (n=470). The reporting quality of the survey studies was poor overall, with 43% of items not reported and 22% of items partially reported. Only one study (8%) explicitly used an objective questionnaire to assess EBP competencies. The proportion of studies reporting on each competency were: 17% on the formulation of clinical questions, 83% on searching the literature, 75% on methodological quality or critical appraisal, 58% on interpreting statistical results, and 75% on applying study results. In general, the six competencies were incompletely defined or reported (e.g., it was unclear what applicability and critical appraisal referred to, and what study designs were appraised by the participants). Two core competencies, the magnitude (size) of effects and the certainty of evidence for effects, were not assessed. ConclusionsAmong 12 included articles the overall quality of study reports was poor, and when EBP competencies were reported they were predominantly self-perceived assessments as opposed to objective assessments. No studies reported on competencies in assessing magnitude of effect or certainty of evidence, skills that are essential for optimizing clinical nutrition decision-making. Systematic review registrationPROSPERO CRD42022311916.

Background/ObjectivesAssessment of energy requirements and intake is central to the nutrition care process, yet current practices among registered dietitians (RDs) are not well characterized. This study examined how RDs assess energy requirements and intake, including perceived accuracy and resources, and differences by setting and experience. MethodsA cross-sectional bilingual online survey was administered to RDs in Canada. The survey collected information on practice setting and experience, access to variables influencing energy requirements/intake, tool use, and opinions on accuracy and resource needs. Descriptive statistics and comparisons were made by practice setting (clinical, community, other) and years in practice (<5, 5-10, >10 years). Results212 RDs completed the survey (62% clinical, 16% community, 22% other settings; 36% <5 years, 23% 5-10 years, 42% >10 years of practice). Participants rated importance of assessing energy requirements and energy intake as moderately high (6.8{square}{+/-}{square}2.2, 7.1{square}{+/-}{square}2.3 out of 10, respectively) and had regular access to variables needed to calculate energy requirements and intake (e.g., age, sex, weight, disease), although access to body composition, sleep, and stress was limited. Commonly-used tools included body weight-based equations and 24-hour recalls. Confidence was highest for delivering interventions and lowest for assessing intake (p < 0.001), especially among less experienced RDs (p = 0.002). Most respondents expressed interest in improved tools for assessing energy requirements (76%) and intake (74%). ConclusionCurrent RD practices vary, and access to key data is limited, underscoring the need for validated, accessible tools and training to support accurate energy assessment in dietetic care.

BackgroundThe interaction between dietary (and supplementary) divalent ions has been a long- standing issue in human nutrition research. Developing optimal calcium and iron supplementation recommendation needs detailed knowledge of the potential trade-offs between: a) the clinical effects of concurrent intake on iron absorption and hematological indices, and b) the potentially negative effects of separated ingestion on adherence to either or both iron and calcium supplements. Human clinical studies have examined the effects of calcium intake on iron status, but there are no meta-analyses or recent reviews summarizing the findings. ObjectiveWe aimed to summarize the literature on the effect of calcium consumption from meals and supplements on iron indices in humans, and quantify the pooled effects. DesignPeer-reviewed randomized and case-cross-over studies were included in this review. ResultThe negative effect of calcium intake was statistically significant in short-term iron absorption studies but the effect magnitude was low (weighted mean difference (WMD) = -5.57%, (95% CI: -7.09, -4.04)). The effect of calcium on iron status was mixed. There was a quadratic dose-response relationship between calcium intake and serum ferritin concentration. Higher daily calcium intake was associated with a modest reduction in serum ferritin concentration. There was, however, no reduction in hemoglobin concentration (WMD = 1.22g/L, 95% CI: 0.37, 2.07). ConclusionThe existing body of studies is insufficient to make recommendations with high confidence due to heterogeneity in design, limitations of ferritin as an iron biomarker and lack of intake studies in pregnant women. Prescribing separation of prenatal calcium and iron supplements in free living individuals is unlikely to affect the anemia burden. There is a need for effectiveness trials comparing the effects of prescribing separated intake to concurrent intake, with functional end-points as primary outcomes, and adherence to each supplement as intermediate outcomes.

BackgroundMaternal vitamin status preconception and during pregnancy have important consequences for pregnancy outcome and offspring development. Changes in status from preconception to early and late pregnancy and postpartum have been inferred from cross-sectional data, with lower pregnancy concentrations often ascribed to plasma volume expansion, but without truly longitudinal data from preconception through pregnancy and post-delivery, and sparse data on the influence of supplementation. This study characterized longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6-months post-delivery, and determined the influence of supplementation. Methods and FindingsBetween 2015-2017, 1729 UK, Singapore and New Zealand women aged 18-38 years planning conception were recruited from the community to a double-blind controlled trial and randomized to a standard (control) or an intervention supplement preconception and throughout pregnancy. Vitamins common to both supplements were folic acid and {beta}-carotene, with the intervention additionally including riboflavin, vitamins B6, B12 and D in amounts available in over-the-counter supplements, alongside iron, calcium and iodine (control and intervention) and myo-inositol, probiotics and zinc (intervention only). We measured maternal plasma concentrations of B-vitamins, vitamin D and insufficiency/deficiency markers (homocysteine, hydroxykynurenine-ratio, methylmalonic acid), at recruitment and 1-month after commencing intervention preconception, in early and late pregnancy, and post-delivery (6-months after supplement discontinuation). From all timepoint data, we derived standard deviation scores (SDS) to characterize longitudinal changes in controls and differences between control and intervention participants. At recruitment preconception, significant proportions had marginal or low plasma status for folate (29.2% <13.6 nmol/L), riboflavin (7.5% <5 nmol/L, 82.0% [&le;]26.5 nmol/L), vitamin B12 (9.1% <221 pmol/L) and vitamin D (48.7% <50 nmol/L). Among controls, plasma concentrations showed differing longitudinal patterns from preconception; riboflavin fell through early/late pregnancy, 25-hydroxyvitamin D was unchanged in early pregnancy, and vitamin B6 and B12 concentrations declined through pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation, with 54.2% developing a low late pregnancy vitamin B6 (pyridoxal 5-phosphate <20 nmol/L). Preconception, the control/intervention groups had similar baseline vitamin concentrations; 1-month after supplement commencement, plasma concentrations became substantially higher in intervention participants; riboflavin by 0.77 SDS (95%CI 0.68-0.87), vitamin B6 1.07 (0.99-1.14), vitamin B12 0.55 (0.46-0.64) and vitamin D 0.51 (0.43-0.60), with the higher levels maintained during pregnancy and marked reduction in insufficiency/deficiency markers (lower homocysteine, hydroxykynurenine-ratio, methylmalonic acid) and the late pregnancy prevalence of vitamin D <50 nmol/L reduced from 35.1% to 8.5%. Plasma vitamin B12 was still higher in the intervention group 6-months post-delivery. ConclusionSignificant proportions of preconception women have marginal or low status of folate, riboflavin, vitamin B12 and vitamin D, and many develop markers of vitamin B6 deficiency in late pregnancy. In the absence of supplementation, maternal plasma vitamin concentrations show differing longitudinal patterns from preconception to early and late pregnancy, suggesting plasma volume expansion does not wholly account for lower gestational concentrations. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of deficiency/depletion markers before and during pregnancy, and a higher maternal plasma vitamin B12 was maintained during the recommended lactational period.

The I-STARCH (Indian Study to Assess Real-World CarboHydrate Consumption) investigation quantified decadal changes in macronutrient intake and carbohydrate quality among Indian adults by benchmarking a 2025 multicentric cross-sectional survey against STARCH 2014. A total of 1,104 adults were enrolled from twenty-nine healthcare centres across fourteen Indian states. Each participant completed three non-consecutive 24 h dietary recalls, harmonised using the ICMR-NIN Food Composition Tables. Temporal contrasts treated 2014 cohort means as fixed benchmarks. In 2025, carbohydrates contributed 62.1% of total energy (2014: 65.8%), fat 25.1% (2014: 21.4%), and protein 12.8% (2014: 12.8%). Carbohydrate quality declined, with simple sugars comprising 20.3% of total carbohydrate (2014: 10.5%) and fibre providing only 1.8% of energy. Across all geographic zones including north, south, east, and west, macronutrient patterns remained suboptimal, indicating persistent dietary imbalance regardless of regional cereal dominance. Adults with type 2 diabetes reported lower carbohydrate intake (61.0%E) than those without diabetes (64.1%E), although both exceeded the recommended 50-55%E range. The composite Diet-Quality Index (protein%E + fibre%E - simple carbohydrate%E; higher = better) was lower in 2025, reflecting refined carbohydrate substitution without improvements in fibre or protein density. A secondary Protein-Fat Quality Index (PFQI = Protein % E / Fat % E) was also computed to assess balance between protein and fat energy. These findings indicate a continuing nutrition transition in India, characterised by persistent carbohydrate predominance, higher dietary fat, and declining carbohydrate quality. Region-specific dietary policies and clinical practices that promote fibre and protein-rich foods, complex carbohydrate sources, and balanced macronutrient quality are needed to support better metabolic health in India.

BackgroundVitamin D has been widely promoted for bone health through supplementation and fortification of the general population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and explore predictive factors for their direction and strength. Methods and analysisWe searched PubMed, EMBASE and CINAHL databases for vitamin D guidelines for the last 10 years. We aim to perform descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association recommendations and AGREE II domains scores and pre-specified characteristics. Ethics and disseminationThis is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers. We intend to publish our results in a suitable, peer-reviewed journal.

BackgroundFortification, the addition of essential micronutrients during food processing, reduces mortality and malnutrition. Our objective was to comprehensively synthesize global evidence on the cost-effectiveness (CE) and cost savings of food fortification. MethodsWe employed systematic review methodology, PROSPERO registration (CRD42023493795), searching six databases to January 2024. Eligible studies included economic analyses comparing staple food post-harvest micronutrient fortification to no fortification. Quality appraisal used Philips modeling framework. We converted incremental cost-effectiveness ratios (ICERs) to 2022 US$; and synthesized the data overall and by micronutrient. For illustration, findings were also categorized by "hypothetical" CE thresholds based on common example percentages of gross domestic product per capita (GDP pc) per country. FindingsAfter screening 6,425 abstracts, 56 studies in 66 reports were included, reporting >200 analyses. Sixty-three countries were represented, including >40 low- and middle-income economies (LMICs). Most frequent interventions were: vitamin A, folic acid, iron, and iodine added to cereal grains/products (e.g., flours) and condiments (e.g., oils, sugar, salt). Models were heterogeneous and employed various perspectives. Most evaluations (58%; 135/232) had ICERs less than $150 per disability-adjusted life year (DALY) averted (or healthy life year gained). We found 87% (201/232) overall were within a hypothetical CE threshold of "50% GDP pc". With an example "35% GDP pc" level among LMICs, 84% (190/227) were estimated to be cost-effective; and 71% (37/52) were less than "20% GDP pc" among low-income countries. Additionally, six out of eight cost-utility studies ICERs were dominant. Moreover, 47 total unique benefit-cost ratios found benefits outweighed costs, ranging from 1{middle dot}50:1 to 100{middle dot}6:1. InterpretationFood fortification programs are likely cost-effective in the majority of contexts. While cost-effectiveness evaluations are specific to local factors and methodology, this research can assist with evidence-informed decision-making for global health policy and priority setting, particularly in resource-constrained economies. FundingU.S. Agency for International Development. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDatabase searches of MEDLINE, Embase, EconLit, and the National Health Service Economic Evaluation Database (NHS EED), from inception to January 2024, were conducted for previous systematic reviews on the economics of food fortification. No language, date, or publication status limits were applied. While the impact of food fortification on health outcomes has been widely studied, we did not find a comprehensive systematic review of the cost-effectiveness of all types of large-scale food fortification. Several smaller systematic reviews and some in-depth narrative reviews have studied the economics of food fortification but their aims were not broad evaluations of its cost-effectiveness as they limited their scope to specific foods or nutrients. Added value of this studyThis large systematic review of 56 economic studies reporting over 200 analyses provides a substantially broader synthesis of the economic evidence base of food fortification. Of note, it also spans 63 countries, including >40 low- and middle-income economies (LMICs), thereby augmenting the international research on a system-level intervention for reducing global malnutrition, mortality, and morbidity. We found that food fortification programs are likely cost-effective in the majority of contexts. Overall, across the many diverse economic models, incremental cost-effectiveness ratios (ICERs) for most evaluations (58%; 135/232) were less than $150 per disability-adjusted life year (DALY) averted (or healthy life year gained). As an illustration using a "hypothetical" cost-effectiveness threshold example of 35% of gross domestic product (GDP) per capita among LMICs, 84% (190/227) of ICERs were estimated to be cost-effective. Additionally, six out of eight cost-utility studies (i.e., measuring quality-adjusted life years, QALYs) ICERs were dominant (i.e., fortification was less costly and more effective than the comparator). Moreover, 47 benefit-cost ratios found that food fortification programs benefits outweighed the costs (with ranges from 1{middle dot}50:1 to 100{middle dot}6:1). Implications of all the available evidenceThere are significant policy implications from this research. The decision by policymakers to enact or strengthen food fortification programs in their countries is predicated by many factors, including costs and cost-effectiveness. Synthesizing the evidence of the economic implications of food fortification could translate to improved global advocacy efforts by partners seeking to introduce and scale up food fortification programs. Nutrition for Growth aims to mobilize governments, bilateral agencies, private investors, businesses, civil society, donors, and others to increase and sustain their funding for nutrition actions, especially those that are evidence-based. Through the Global Nutrition Report, such financial commitments are being tracked internationally. The expectation is that this more robust evidence base of the cost-effectiveness of large-scale food fortification will encourage greater investment in initiating and strengthening fortification programs where they are needed. While cost-effectiveness evaluations are specific to local factors and methodology, this research can assist with evidence-informed decision-making for global health policy and priority setting, particularly in resource-constrained economies.

Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as potential risk factors for poor iron status. Our objective was to examine the association between pre-pregnancy BMI and iron status in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n=1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cooks equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted Poisson regression models, adjusted for confounders (age, race/ethnicity, education, family income, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR)=1.28, 95%CI: 0.89-1.83; obesity, PR=0.75, 95%CI: 0.39-1.45; anemia: overweight, PR=1.08, 95%CI: 0.53-2.19; obesity, PR=0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that iron status in pregnancy does not differ by pre-pregnancy BMI. Since iron deficiency during pregnancy remains a significant public health concern, NHANES should consider measuring current iron status in upcoming cycles.

BackgroundMaternal nutritional interventions aim to address nutrient deficiencies in pregnancy, a leading cause of maternal and neonatal morbidity and mortality worldwide. How these interventions influence the placenta, which plays a vital role in fetal growth and nutrient supply, is not well understood. This is a major gap in understanding how such interventions could influence pregnancy outcomes and fetal health. We hypothesised that nutritional interventions influence placental phenotype, and that these placental changes relate to how successful, or not, the intervention is in improving pregnancy outcomes. MethodsWe conducted a systematic review and followed PRISMA-2020 reporting guidelines. Articles were retrieved from PubMed, Clinicaltrials.gov, and ICTRP-WHO using pre-defined search terms and screened by two reviewers using a 3-level process. Inclusion criteria considered articles published from January 2001-September 2021 that reported on clinical trials in humans, which administered a maternal nutritional intervention during the periconceptional or pregnancy period and reported on placental phenotype (shape and form, function or placental disorders). FindingsFifty-three eligible articles reported on (multiple) micronutrient- (n=33 studies), lipid- (n=11), protein- (n=2), and diet-/lifestyle-based (n=8) interventions. Of the micronutrient-based interventions, 16 (48%) associated with altered placental function, namely altered nutrient transport/metabolism (n=9). Nine (82%) of the lipid-based interventions associated with altered placental phenotype, including elevated placental fatty acid levels (n=5), altered nutrient transport/metabolism gene expression (n=4), and decreased inflammatory biomarkers (n=2). Of the protein-based interventions, two (66%) associated with altered placental phenotype, including increased placental efficiency (n=1) or decreased preeclampsia risk (n=1). Three (38%) of diet and lifestyle-based interventions associated with placental changes, namely placental gene expression (n=1) and disease (n=2). In studies with data on maternal (n=30) or offspring (n=20) outcomes, interventions that influenced placental phenotype were more likely to have also associated with improved maternal outcomes (11/15 [73%]) and offspring birth outcomes (6/11 [54%]), compared to interventions that did not associate with placental changes (2/15 [13%] and 1/9 [11%], respectively). ConclusionsPericonceptional and prenatal nutritional interventions to improve maternal/pregnancy health associate with altered placental development and function. These placental adaptations likely benefit the pregnancy and improve offspring outcomes. Understanding the placentas role in the success of interventions to combat nutrient deficiencies is critical for improving interventions and reducing maternal and neonatal morbidity and mortality globally.

BackgroundBoth small-quantity (SQ) and medium-quantity (MQ) lipid-based nutrient supplements (LNS) have been used for prevention of child undernutrition. A meta-analysis of 14 trials of SQ-LNS vs no LNS showed effects on length-for-age (LAZ, +0.14 (95% confidence interval 0.11, 0.16)) and weight-for-length (WLZ, +0.08 (0.06, 0.10)) z-scores, as well as prevalence ratios (95% CI) for stunting (LAZ<-2, 0.88 (0.85, 0.91)) and wasting (WLZ < -2, (0.80, 0.93)). However, little is known about the effects of MQ-LNS on growth. ObjectiveWe aimed to examine the effects of preventive MQ-LNS ([~]250-499 kcal/d) provided at [~]6-23 mo of age on growth outcomes compared to no LNS or provision of SQ-LNS. MethodsWe conducted a systematic review of studies of MQ-LNS for prevention, and categorized them as providing < 6 mo vs. > 6 mo of supplementation; for the latter category we conducted a meta-analysis, with main outcomes being change in WLZ and LAZ, and prevalence of wasting and stunting. ResultsThree studies provided MQ-LNS for 3-5 mo (seasonal) for children 6-36 mo of age, and did not show consistent effects on growth outcomes. Eight studies provided MQ-LNS for 6-18 mo, generally starting at 6 mo of age; in the meta-analysis (max total n=13,673), MQ-LNS increased WLZ (+0.09 (0.05, 0.13)) and reduced wasting (0.89 (0.81, 0.97)), but had no effect on LAZ (+0.04 (-0.02, 0.11)) or stunting (0.97 (0.92, 1.02)) compared to no LNS. Two studies directly compared SQ-LNS and MQ-LNS and showed no significant differences in growth outcomes. ConclusionsThe current evidence suggests that MQ-LNS offers no added benefits over SQ-LNS, although further studies directly comparing MQ-LNS vs. SQ-LNS would be useful. One possible explanation is incomplete consumption of the MQ-LNS ration and thus lower than desirable intake of certain nutrients. RegistryPROSPERO CRD42022382448: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382448

BackgroundProbiotics may enhance host iron bioavailability, offering a strategy to address iron deficiency. Fecal iron may be a useful non-invasive biomarker of such effects in infants. ObjectiveTo examine the use of fecal iron quantification in a randomized placebo-controlled trial (RCT) of neonatal administration of Lactiplantibacillus plantarum ATCC 202195 (LP202195), with or without fructooligosaccharide (FOS), in Dhaka, Bangladesh. MethodsFecal iron quantification using atomic absorption spectrometry (AAS) was optimized using standards and reference materials, and pilot-tested using pooled stool aliquots (n=32) from an observational cohort of young infants in Bangladesh (aged 0-64 days). The optimized AAS assay was then applied to individual stool samples collected at 14 days of age (n=307) in a RCT in which newborns aged 0-4 days were randomly allocated to one of five groups: placebo, 1-or 7-day regimens of LP202195, with or without FOS. Serum ferritin was measured at 2 months postnatal age (n=251). Effects of the 1-and 7-day LP202195 regimens were estimated using linear regression and expressed as mean percent differences relative to placebo, with 95% confidence intervals (95%CI). ResultsThe optimized AAS fecal iron assay had acceptable accuracy (91-99%), precision (within-and between-run coefficients of variation <10%), and recovery (93-112%), with a reportable range of 0.2 to 80 mg Fe per 100 g dry stool. In pooled samples from the observational cohort, fecal iron varied with age and feeding status. In the RCT, fecal iron concentrations did not significantly differ following1-day (% difference=9.8%, 95%CI:-19%, 49%; P=0.54) or 7-days (% difference=-6.1%, 95%CI:-31%, 28%; P=0.69) of LP202195 administration, versus placebo (geometric mean concentration=4.3mg Fe/100g dry stool (95%CI:3.3, 5.6); n=53). Inferences were unchanged when groups were disaggregated by FOS co-administration (P>0.05 for all). Similarly, there were no effects of LP202195 on serum ferritin at 2 months of age (P>0.05 for all). ConclusionsFecal iron quantification by AAS was valid and feasibly implemented in a trial of neonatal administration of Lactiplantibacillus plantarum ATCC 202195. However, the assay is resource-intensive and may not be more informative than conventional measures of iron status when studying the effects of probiotics/synbiotics on iron bioavailability. Clinical Trial RegistryClinicalTrials.gov identifier: NCT05180201

BackgroundModerate acute malnutrition (MAM) remains a major health challenge in India despite ongoing efforts of government nutrition programs. Finger millet (Ragi), a nutrient-dense, climate-resilient crop rich in calcium, fiber, and bioactive compounds, offers potential advantages over conventional cereal-based ready-to-use therapeutic foods (RUTF). This trial evaluated the effects of finger millet-based supplement on anthropometry, body composition, dietary adequacy among MAM children aged 18-59 months. Material & methodsIn this open-label, randomized community-based trial, 221 MAM children were allocated to receive either a finger millet-with-dates supplement (FMD) or the standard wheat/rice-based Balamrutham plus with dates (BMD) for 8 weeks in Anganwadi centers in Hyderabad, India. Anthropometry, body composition (InBody S10), dietary intake (three-day recall), biomarkers, and compliance were assessed at baseline and endpoint, with follow-ups at days 100 and 160. Growth trends were evaluated using repeated-measures ANOVA. Results136 children completed the intervention (FMD: 71; BMD: 65); compliance exceeded 80%. By day 40, both groups showed significant gains in weight (6.3-6.4%), height (2.4%), and MUAC (3.5-6.2%), which continued through day 160. The FMD group showed greater improvements in mineral mass, bone mineral content, and skeletal muscle mass, whereas the BMD group demonstrated higher increases in protein mass and fat-free mass. Dietary recall revealed markedly low micronutrient adequacy among MAM children. No major adverse events were reported. ConclusionFinger millet-based supplementation achieved comparable or superior improvements to cereal-based RUTF, supporting its integration into ICDS and POSHAN 2.0 as a sustainable approach to MAM management.

BackgroundEvidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease, such as offspring telomere length (TL) and mitochondrial DNA content (mtDNAc) is unknown. ObjectivesWe assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome. DesignWe conducted a randomized controlled trial in rural Burkina Faso, among pregnant females (15-40 years old) enrolled at <21 weeks of gestation. Mothers received either MMN-fortified BEP and IFA (intervention) or IFA only (control) throughout pregnancy. Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants, respectively. Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction. Linear regression models were fitted to assess TL and mtDNAc differences across trial arms. ResultsWe found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL [{beta} = -0.010 (95% CI: -0.057, 0.036); P = 0.662] or mtDNAc [{beta} = 0.065 (95% CI: -0.203, 0.073); P = 0.354], as compared to an IFA tablet alone. These findings were confirmed (P >0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher, but non-significantly different mtDNAc among children born either small-for-gestational age, low birthweight, or preterm. ConclusionsNewborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.

ObjectiveThis systematic review evaluates whether vitamin D and calcium supplementation benefits Chronic kidney disease (CKD) patients Quality of Life (QoL) and Renal function. BackgroundCKD disrupts calcium-phosphate homeostasis, leading to secondary hyperparathyroidism and bone mineral disorders. Efficacy of vitamin D and calcium supplementation in managing CKD remains controversial. MethodsPubMed, Google Scholar, Science Direct and EBSCO were searched from October 2024 to February 2025. Fifteen out of 82 identified studies were included. Data quality was assessed using Critical Appraisal Skills Programme (CASP) while bias risk was visualized using Robvis. Estimated Glomerular Filtration Rate (eGFR) and Parathyroid Hormone (PTH) outcomes were analysed using meta-analysis, whereas Bone Mineral Density (BMD) and Quality of Life (QoL) were assessed through narrative synthesis. ResultsVitamin D supplementation had no significant effect on eGFR (MD=0.84mL/min/1.73m{superscript 2},95%CI: -0.47 to 2.15, p=0.207) or PTH levels (MD = -6.76,95%CI: -34.92 to 1.95, p=0.005). No significant differences were found between active and inactive vitamin D supplementation on kidney function, while the results for BMD and QoL were inconclusive. ConclusionVitamin D supplementation had no significant effects on kidney function or QoL. Limited data precluded conclusions about calcium supplementation. Future studies are needed to clarify the roles of these treatments on CKD. Trial Registration NumberPROSPERO registration CRD42024607320. O_LIWhat is already known on this topic - Chronic Kidney Disease is a known progressive condition that affects over 10% of the global population. One of the most significant complications of CKD is the disruption if the calcium and phosphate balance, leading to conditions like secondary hyperparathyroidism. These complications can cause a significant impairment on the QoL of CKD patients. Vitamin D supplementation has become a standardised therapy for management of these complications, however there is a lack of clinical evidence in the effectiveness of these treatments. C_LIO_LIWhat this study adds - Despite the fact that vitamin D supplements are widely recommended to CKD patients, the evidence from the studies included in this systematic review showed no statistically significant effects. Furthermore, this review highlights the limited research on the effects of calcium supplementation, specifically in combination with vitamin D supplementation. C_LIO_LIHow this study might affect research, practice or policy - This systematic review highlights the need for more rigorous clinical trials to assess the safety and efficacy of vitamin D and vitamin C supplementation in CKD patients. This research should also explore the long term effects and determine the impact of these treatments at different stages of CKD to determine whether these treatments are more effective at certain stages of the disease. C_LI

BackgroundSkeletal muscle wasting is a major determinant of physical functional disability in critical illness survivors, and contributes to post-intensive care syndrome. As yet, no therapies exist to address this major public health issue. Intramuscular bioenergetic failure and inflammation are understood to be the underpinning mechanisms, and carbohydrate and lipid oxidation are impaired. This systematic review synthesises the evidence that peroxisome proliferator-activated receptor gamma agonists may be a therapeutic option to optimise clinical nutrition in critically ill patients. MethodSystematic review and meta-analysis. ResultsFourteen studies over 19 publications were included. Lean body mass was unaffected (n=174). Pioglitazone treatment resulted in periperal insulin sensitivity increasing 30-71% (Standardised mean change 0.97 (95%CI 0.36-1.58; n=213). Intramuscular Tumour Necrosis Factor Alpha concentrations decreased in treatement arms (n=29) as did circulating interlukin-6 and Tumour Necrosis Factor Alpha (n=53). Intramyocellular Lipid concentrations decreased by 34-40% with pioglitazone therapy (n=60). Treatment increased intramuscular markers of Oxidative Phosphorylation (n=55), mitochondrial biogenesis(PGC1 and PGC1{beta}; n=26) and {beta}-oxidation (n=29) ConclusionsPioglitazone therapy increases skeletal muscle insulin sensitivity, decreases intramyocellular lipid accumulation and systemic and intramuscular inflammation. Where lean body mass was measured, this was seen to increase. Pioglitazone may be an adjunctive therapy to optimise clinical nutrition in acutely unwell patients. Clinical relevancy statementPioglitazone may optimise clinical nutrition therapy in critically ill patients by normalising carbohydrate and lipid metabolism.

IntroductionTraditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can co-exist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A status and weight status (both under- and overweight) in children and young people. MethodsOvid Medline, Ovid Embase, Scopus, and Cochrane databases were systematically searched for observational studies assessing micronutrient status (blood, serum, or plasma levels of iron, zinc, or vitamin A biomarkers) and weight status (body mass index or other anthropometric measurement) in humans under 25 years of any ethnicity and gender. Risk of bias assessment was conducted using the American Dietetic Association Quality Criteria Checklist. Where possible, random effects restricted maximum likelihood (REML) meta-analyses were performed. PROSPERO (CRD42020221523). ResultsAfter screening, 83 observational studies involving 190,443 participants from 44 countries were identified, with many studies having reported on more than one micronutrient and/or weight status indicator. Iron was the most investigated micronutrient, with 46, 28, and 27 studies reporting data for iron, zinc, and vitamin A status, respectively. Synthesizing 16 records of odds ratio (OR) from 7 eligible studies, overnutrition (overweight and obesity) increased odds of iron deficiency (OR [95%CI]: 1.51 [1.20, 1.82], p<0.0001, I2=40.7%). Odds appeared to be higher for children living with obesity (1.88 [1.33, 2.43], p<0.0001 I2=20.6%) in comparison to those with overweight (1.31 [0.98, 1.64], p<0.0001 I2=40.5%), although between group differences were not significant (p=0.08). ConclusionsOvernutrition is associated with increased risk of iron deficiency, but not zinc or vitamin A deficiencies, with an inverted U-shaped relationship observed between iron status and bodyweight. Our results highlight significant heterogeneity in the reporting of micronutrient biomarkers and how deficiencies were defined. Inflammation status was rarely adequately accounted for, and the burden of iron deficiency may well be under-recognised, particularly in children and young people living with overnutrition. Key questionsO_ST_ABSWhat is already known on this topicC_ST_ABS-summarise the state of scientific knowledge on this subject before you did your study and why this study needed to be done O_LILow-and middle-income countries are increasingly facing a double burden of malnutrition; that is, the coexistence of undernutrition (stunting, wasting, underweight) with overnutrition (overweight and obesity). C_LIO_LIWhile the relationship between undernutrition and critical micronutrients for childhood growth and development (e.g., iron, zinc, and vitamin A) is well established, less is known about the risk of micronutrient deficiencies in children and adolescents with overweight or obese, a hidden form of malnutrition. C_LIO_LIThere are limited data summarising associations between biomarkers of the most commonly limiting micronutrients and body weight status, particularly in children and young people. C_LI What this study adds-summarise what we now know as a result of this study that we did not know before O_LIOvernutrition increases the risk of iron deficiency, but not zinc or vitamin A deficiencies. C_LIO_LIThere is an inverted U-shaped relationship observed between iron status and bodyweight in children and young people, with iron deficiencies observed more frequent in both under- and overnutrition. C_LIO_LIStudies done to date have been heterogeneous in terms of populations studied, diagnostic criteria, and approaches to data analysis; few followed current guidelines for measuring inflammation and defining micronutrient deficiencies. C_LI How this study might affect research, practice or policy-summarise the implications of this study O_LIIncreased recognition by healthcare practitioners that children and young people living with overweight, or obesity are likely to be iron deficient; thereby improving clinical practice and care. C_LIO_LIThe gaps in evidence highlighted are addressed, with more research from currently underrepresented counties examining micronutrient deficiencies and the double burden of malnutrition. C_LIO_LIThe weaknesses in study design and reporting highlighted are addressed, with improved quality and reporting of micronutrient assessment in children and young people. C_LI

Vitamin D is essential for bone and metabolic health. Deficiency remains a global health issue, particularly among older adults and ethnic minorities with darker skin pigmentation. Data on circannual variation these groups remain sparse. This study reports vitamin D status in older adults ([&ge;]65 years) and ethnic adults ([&ge;]18 years, Fitzpatrick classes IV-VI) in northern Britain during the screening phase of a supplementation trial. Participants were screened for inclusion between December 2024 and August 2025. Serum 25-hydroxyvitamin D (25(OH)D) was assessed in dried blood spots followed by LC-MS/MS analysis. 299 participants were screened. Vitamin D insufficiency or deficiency (<50 nmol/L) was noted in 54.8% of older adults and 72.1% of ethnic individuals. These rates did not decline during summer months. These findings highlight persistently high rates of vitamin D insufficiency across high-risk groups in northern Britain and underscore the inadequacy of sunlight exposure as a corrective measure.