RATIONALE:Vitamin B12 deficiency is an important public health problem in children, and has been associated with anaemia and impaired growth, cognition, and development. Vitamin B12 deficiency may develop in children due to lower content in breast milk, low dietary intake, and as requirements increase with age. Vitamin B12 supplementation may confer benefits to child growth and development, due to its role in DNA synthesis and methylation, red blood cell formation, and folate metabolism. However, no systematic reviews have been conducted to examine the effects of vitamin B12 supplementation in children. OBJECTIVES:To determine the effects of vitamin B12 supplementation on growth, development, and cognition in children less than 12 years of age. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, 12 other databases, and two trial registries on 23 September 2025. We screened reference lists of studies. ELIGIBILITY CRITERIA:We included randomised controlled trials evaluating the effects of oral vitamin B12 supplementation, alone or in combination with other micronutrients, in children < 12 years of age. We excluded cross-over trials, trials targeting pregnant or breastfeeding women, or participants with critical illnesses, and interventions delivered by intravenous/intramuscular injections. OUTCOMES:Critical outcomes were vitamin B12 status, anaemia, haemoglobin, growth, cognitive function, developmental outcomes, and any adverse effects. Important outcomes included megaloblastic anaemia, body composition, health-related quality of life, morbidity, and all-cause mortality. RISK OF BIAS:We used Cochrane RoB 2 to evaluate bias. SYNTHESIS METHODS:We conducted meta-analyses using fixed-effect models. If there was substantial heterogeneity, we used random-effect models. When meta-analyses were not conducted, we described findings from individual trials, and considered synthesis and presentation of findings using other methods. We used GRADE to evaluate the certainty of evidence for critical outcomes. INCLUDED STUDIES:We included 16 trials (4083 children; 2 days to 11 years) in 10 countries, including India, Japan, Thailand, Nepal, United Kingdom, Italy, Spain, the United States, El Salvador, and Guatemala. Follow-up periods for outcomes in most studies ranged from five weeks to 31 months, with one study extending follow-up to nine years. Duration of vitamin B12 supplementation varied, ranging from 28 days to 31 months, with doses from 0.9 µg/day to 150 µg/day. Nine trials, including 2391 children, contributed data to meta-analyses. SYNTHESIS OF RESULTS:Supplementation with vitamin B12 alone versus placebo There may be little to no difference between groups in height/length (mean difference (MD) -0.19 cm, 95% confidence interval (CI) -2.44 to 2.06; 2 trials, 143 children; low-certainty evidence). There may be little to no difference between groups in cognitive function (e.g. attention) (standardised mean difference (SMD) 0.09, 95% CI -0.10 to 0.28; 2 trials, 438 children, low-certainty evidence). There may be little to no difference between groups in motor skill development (6 to 9 years, NEuroPSYchological assessment, Second Edition (NEPSY-II); 1 trial, 403 children, low-certainty evidence). Vitamin B12 supplementation in children reduces vitamin B12 deficiency (absolute risk difference (ARD) 56 fewer per 1000, 95% CI 68 fewer to 24 fewer; 1.8% versus 7.6%; risk ratio (RR) 0.27, 95% CI 0.11 to 0.69; 3 trials, 642 children; high-certainty evidence), and probably increases total vitamin B12 concentrations (MD 68.53 pmol/L, 95% CI 41.83 to 95.23; 7 trials, 705 children; moderate-certainty evidence), compared to placebo, with an average increase of 68.5 pmol/L. There may be little to no difference between groups in anaemia (ARD 21 more per 1000, 95% CI 26 fewer to 191 more; 9.1% versus 4.5%; RR 1.48, 95% CI 0.41 to 5.27; 2 trials, 144 children; low-certainty evidence). No trials reported the occurrence of any adverse effects. Supplementation with vitamin B12 alone versus no intervention The evidence is very uncertain about the effects of vitamin B12 on height/length (2 trials, 70 children; very low-certainty evidence), compared to no intervention. No trials reported data for the other critical outcomes. Supplementation with vitamin B12 and other micronutrients, compared to the same formulation without vitamin B12 There may be little to no difference between groups in height/length (MD -0.22 cm, 95% CI -0.65 to 0.20; 2 trials, 608 children; low-certainty evidence). There may be little to no difference between groups in cognitive function (e.g. attention) (SMD 0.00, 95% CI -0.13 to 0.13; 3 trials, 956 children; low-certainty evidence). There may be little to no difference between groups in development outcomes (e.g. motor skill development) (SMD -0.05, 95% CI -0.18 to 0.08; 2 trials, 960 children; low-certainty evidence). Children who received vitamin B12 supplementation and other micronutrients may have little to no difference in vitamin B12 deficiency (ARD 2 fewer per 1000, 95% CI 7 fewer to 32 more; 0.7% versus 0.8%; RR 0.77, 95% CI 0.12 to 5.16; 2 trials, 534 children; low-certainty evidence), or total vitamin B12 concentrations (MD 34.32 pmol/L, 95% CI -31.13 to 99.77; 3 trials, 731 children; low-certainty evidence), compared to supplements without vitamin B12. There may be little to no difference between groups in anaemia (21.7% versus 25.0%; 1 trial, 35 children; low-certainty evidence). There may be little to no difference between groups in any adverse effects (9.2% versus 5.9%; 1 trial, 574 children; low-certainty evidence). The certainty of evidence for critical outcomes ranged from high to very low; we downgraded for imprecision due to small sample sizes or few events, risk of bias in outcome measurement, randomisation methods, selective reporting bias, or inconsistency due to substantial statistical heterogeneity. Few studies reported growth, cognition, development, anaemia, or any adverse effects. AUTHORS' CONCLUSIONS:Vitamin B12 supplementation (alone or when supplemented with other micronutrients) in children may have little to no effect on growth (i.e. height/length), cognitive function (e.g. attention), development outcomes (e.g. motor skill development), or anaemia, compared to placebo, no intervention, or the same supplements without vitamin B12. Vitamin B12 supplementation in children reduces vitamin B12 deficiency and probably improves total vitamin B12 concentrations, compared to placebo. However, vitamin B12 supplementation with other micronutrients may result in little to no difference in vitamin B12 deficiency and total vitamin B12 concentrations, compared to the same formulation without vitamin B12. FUNDING:This review had no dedicated funding. REGISTRATION:Protocol available via DOI 10.1002/14651858.CD015264.

BACKGROUND AND AIMS:Biofortification of staple crops with higher concentrations of micronutrients via traditional breeding methods is a sustainable strategy and can possibly complement fortification and other interventions to target micronutrient deficiencies in low resource settings, particularly among populations such as children. We aimed to determine if iron- and zinc-biofortified pearl millet (FeZnPM, Dhanashakti, ICTP-8203Fe)-based complementary feeding improves nutritional status, including iron and zinc biomarkers and growth, in children living in urban slums of Mumbai. METHODS:We conducted a randomized controlled trial of FeZnPM among 223 children aged 12-18 months who were not severely anemic at baseline (hemoglobin ≥9.0 g/dL). Children were randomized to receive either FeZnPM or conventional (non-biofortified) pearl millet (CPM) daily for 9 months. Hemoglobin, serum ferritin, and plasma zinc concentrations as well as growth indicators (length, weight, mid-upper arm circumferences, triceps and subscapular skinfolds) were evaluated at enrollment and throughout the trial. World Health Organization (WHO) anthropometric Z-scores were calculated using WHO growth standards. Primary outcomes were hemoglobin and serum ferritin concentrations, and growth, defined as WHO Z-scores. An intent-to-treat approach was used for analyses. We used the Hodges-Lehmann-Sen test to assess the change in primary outcomes between baseline and the last visit and report corresponding 95 % confidence intervals. RESULTS:At baseline, 49.3 % of children had anemia (hemoglobin <10.5 g/dL) and 59.6 % had iron deficiency (serum ferritin <12 μg/L). Consumption of FeZnPM increased hemoglobin concentration compared to CPM [change over time: 0.10 g/dL (-0.60, 0.90) vs. CPM: -0.15 g/dL (-1.00, 0.40) P = 0.04]. After follow-up, FeZnPM did not increase the concentration of serum ferritin or plasma zincor improve growth, compared to CPM (P > 0.05). Though the trial was not designed to detect this difference, the prevalence of anemia at endpoint was 33.8 % among those consuming FeZnPM, compared to 57.6 % in the CPM group (P = 0.005). CONCLUSIONS:Daily consumption of FeZnPM-based complementary foods improved hemoglobin concentrations and reduced prevalence of anemia in children living in Mumbai's urban slums. However, the intervention did not significantly impact serum ferritin, plasma zincor growth outcomes. TRIAL REGISTRATION:This trial is registered with Clinicaltrials.gov (ID: NCT02233764), and Clinical Trials Registry of India (ID: REF/2014/10/007731).

Undernutrition-the leading risk factor for tuberculosis worldwide-is associated with impaired immunity, more extensive disease, delayed sputum conversion, and worse treatment outcomes, including mortality. In this Health Policy, we propose a comprehensive roadmap for integrating nutritional assessment, counselling, and support into tuberculosis treatment as part of person-centred care. At treatment initiation, we recommend standard nutritional assessment with anthropometric measurements and haemoglobin estimation, in addition to macronutrient and micronutrient support alongside nutritional counselling. Weight should be monitored during treatment and lack of weight gain at the end of the intensive phase should prompt an investigation of causes, such as food insecurity, poor treatment adherence, malabsorption, uncontrolled diabetes, or drug resistance. At the end of treatment, we recommend reassessing anthropometric measures to assess nutritional recovery. People with tuberculosis who remain underweight should receive close follow-up to detect early relapse. We call for annual reporting of nutritional metrics by WHO, explicit inclusion of nutritional assessment and care in national strategic plans, domestic or international support of nutritional programmes for people with tuberculosis, increased support for operational research initiatives, and integration of nutritional care into the WHO Multisectoral Accountability Framework at national and regional levels.

BACKGROUND:The epidemic of overweight and obesity affects more than 390 million children and adolescents aged 5 to 19 years and 37 million children under five years of age. Overweight and obesity are associated with both short- and long-term consequences, including chronic inflammation, metabolic diseases, as well as alterations in the gut microbiome composition. Gut microbiome-based approaches may impact microbiome-related metrics such as diversity or the abundance of intestinal bacteria, which may be linked to obesity-related outcomes. However, evidence regarding the effect of gut microbiome-based interventions for the management of obesity is limited. OBJECTIVES:To assess the effects of gut microbiome-based interventions in the management of overweight or obesity in children and adolescents in all their diversity aged 0 to 19 years. SEARCH METHODS:We searched CENTRAL, MEDLINE, CINAHL, Web of Science Core Collection, BIOSIS Previews, Global Index Medicus (all regions), IBECS, SciELO, PAHO, PAHO IRIS, WHO IRIS, WHOLIS, Bibliomap, TRoPHI as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 24 January 2025. We did not apply any language restrictions. SELECTION CRITERIA:We included randomised controlled trials that evaluated gut microbiome-based interventions [i.e. prebiotics, probiotics, synbiotics, short-chain fatty acids (SCFAs), and faecal microbiota transplantation (FMT)] compared to standard-of-care, placebo, or control interventions in children and adolescents aged 0 to 19 years with overweight or obesity. DATA COLLECTION AND ANALYSIS:Two review authors independently screened titles and abstracts and full texts, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool and certainty of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE), a framework for assessing the certainty of evidence and making recommendations in systematic reviews. Random-effects meta-analyses were performed unless only one study per outcome was available, for which fixed-effect analyses were performed. MAIN RESULTS:We found 17 studies (838 participants) from various countries, evaluating the effects of prebiotics, probiotics, synbiotics, SCFAs, and FMT on body mass index (BMI), body weight, waist circumference, total body fat percentage (%TBF), systolic and diastolic blood pressure, and adverse events. Of the 17 studies included, five studies were in adolescents aged 10 to 19 years, and 12 studies were in children and adolescents spanning both age groups, 0 to 19 years. Upon contacting authors for data grouped by age of the participants, no studies provided separate outcomes data for children and adolescents. The included studies were funded by either academic funding sources or grants from the public and private sectors. Additionally, 15 studies were classified as currently being conducted ('ongoing'). The certainty of evidence throughout was very low. In adolescents 10 to 19 years of age, probiotics compared to placebo or no intervention may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events. Similarly, FMT compared to placebo may have little to no effect on waist circumference, %TBF, blood pressure, and adverse events in this age group. According to one study with 41 participants and in children and adolescents 0 to 19 years of age, intervention with prebiotics compared to placebo may result in a small reduction in BMI (mean difference = -0.70, 95% CI = -1.25 to -0.15) and body weight (mean difference = -1.5, 95% CI = -2.61 to -0.39). Prebiotics compared to placebo may have little to no effect on waist circumference, %TBF, systolic blood pressure, and adverse events. No data were available on the effect of prebiotics on diastolic blood pressure. Probiotics compared to placebo may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events in children and adolescents (0 to 19 years). Synbiotics compared to placebo may result in a reduction in systolic blood pressure (mean difference = -40.00, 95% CI = -50.63 to -29.37) in children and adolescents (0 to 19 years); according to one study with 56 participants. The evidence is very uncertain about the effects of synbiotics compared to a placebo on BMI, body weight, waist circumference, blood pressure, and adverse events. No data were available on the effect of synbiotics compared to placebo on %TBF. Synbiotics, compared to probiotics, may have little to no effect on waist circumference, %TBF, and adverse events. No data were available on the effect of synbiotics compared to probiotics on BMI, body weight, and blood pressure. According to one study with 48 participants and very low-certainty of evidence, SCFAs compared to placebo may result in a reduction in waist circumference (mean difference = -5.08, 95% CI = -7.40 to -2.76) and BMI (mean difference = -2.26, 95% CI = -3.24 to -1.28) in children and adolescents (0-19 years). SCFAs compared to placebo may have little to no effect on adverse events. No data were available on the effect of SCFAs on body weight, %TBF, and blood pressure. Adverse events, i.e. abdominal cramps, abdominal discomfort, abdominal pain, diarrhoea, vomiting, and migraine, were reported in the prebiotics group but with very low incidence. Additionally, adverse events such as nausea and headache were reported in the SCFAs group, but with low incidence. AUTHORS' CONCLUSIONS:In adolescents aged 10 to 19 years, gut microbiome-based interventions may result in little to no difference in obesity-related outcomes. In children and adolescents aged 0 to 19 years, prebiotics may result in a small reduction in BMI and body weight; synbiotics may result in a reduction in systolic blood pressure, and SCFAs may result in a reduction in BMI and waist circumference, albeit the certainty of evidence was very low. The evidence was of very low certainty due to few studies per comparison, small sample sizes, short intervention durations, and insufficient reporting of adverse events. More rigorous research examining different types of gut microbiome-based interventions for the management of obesity is required in children and adolescents, both in clinical and community settings. Future trials should also report methods related to randomisation, blinding, and compliance, as well as include prespecified analysis plans.

BACKGROUND:Precision nutrition-based methods develop tailored interventions and/or recommendations accounting for determinants of intra- and inter-individual variation in response to the same diet, compared to current 'one-size-fits-all' population-level approaches. Determinants may include genetics, current dietary habits and eating patterns, circadian rhythms, health status, gut microbiome, socioeconomic and psychosocial characteristics, and physical activity. ​​​​In this systematic review, we examined the evidence base for the effect of interventions based on precision nutrition approaches on overweight and obesity in children and adolescents to help inform future research and global guidelines. OBJECTIVES:To examine the impact of precision nutrition-based interventions for the management of obesity in children and adolescents in all their diversity. SEARCH METHODS:We searched CENTRAL, MEDLINE, CINAHL, Web of Science Core Collection, BIOSIS Previews, Global Index Medicus (all regions), IBECS, SciELO, PAHO, PAHO IRIS, WHO IRIS, WHOLIS, Bibliomap, and TRoPHI, as well as the WHO ICTRP and ClinicalTrials.gov. We last searched the databases on 23 July 2024. We did not apply any language restrictions. SELECTION CRITERIA:We included randomised or quasi-randomised controlled trials that evaluated precision nutrition-based interventions (accounting for 'omics' such as phenotyping, genotyping, gut microbiome; clinical data, baseline dietary intake, postprandial glucose response, etc., and/or including artificial intelligence such as machine learning methods) compared to general or one-size-fits-all interventions or no intervention in children and adolescents aged 0 to 9 years or 10 to 19 years with overweight or obesity. DATA COLLECTION AND ANALYSIS:Two review authors independently conducted study screening, data extraction, and risk of bias and GRADE assessments. We used fixed-effect analyses. Our outcomes of interest were physical and mental well-being, physical activity, health-related quality of life, obesity-associated disability, and adverse events associated with the interventions as defined or measured by trialists, and weight change (reduction, stabilisation or maintenance). MAIN RESULTS:Two studies (3 references, 105 participants) conducted in Ukraine and Greece met our eligibility criteria. One study reported nonprofit funding sources, whilst the other did not report funding, and the certainty of evidence ranged from very low to low across outcomes (all measured at endpoint). Only one trial (65 participants) contributed data on our primary outcomes of interest. Precision nutrition-based intervention versus one-size-fits-all intervention or standard of care In children 0 to 9 years of age, evidence is very uncertain about the effect of a precision nutrition-based intervention (a computerised Decision Support Tool (DST) that incorporates a variety of participant data and provides personalised diet recommendations based on decision-tree algorithms) on body mass index (BMI) (mean difference (MD) -1.40 kg/m2, 95% confidence interval (CI) -3.48 to 0.68; 1 study, 35 participants; very low-certainty evidence) and on weight (MD -2.60 kg, 95% CI -8.42 to 3.22; 1 study, 35 participants; very low-certainty evidence) compared with a one-size-fits-all control intervention. In children and adolescents 10 to 19 years of age, evidence is very uncertain about the effect of a precision nutrition-based intervention (computerised DST) on BMI (MD 3.00 kg/m2, 95% CI -0.26 to 6.26; 1 study, 30 participants; very low-certainty evidence) and on weight (MD 11.40 kg, 95% CI -0.47 to 23.27; 1 study, 30 participants; very low-certainty evidence) compared with a one-size-fits-all control intervention. AUTHORS' CONCLUSIONS:Based on data from two small studies with a total of 105 participants, the evidence is very uncertain about the effect of precision nutrition-based interventions on body weight or BMI. This review was limited by the number of available randomised controlled trials in this relatively nascent field. Given these limitations, the two studies do not provide sufficient evidence to adequately inform practice. Future research should report participant outcome data, including outcomes related to mental, emotional, and functional well-being, in addition to biochemical and physical measures, stratified by World Health Organization-defined age groups (children (0 to 9 years), and children and adolescents (10 to 19 years)). Future studies should also report methods related to randomisation, blinding, and compliance, as well as include prespecified analysis plans.

Two initiatives are reshaping how we can approach and address the persistent and widely prevalent challenge of malnutrition, the leading global risk factor for morbidity and mortality. First is the focus on precision nutrition to identify inter- and intra-individual variation in our responses to diet, and its determinants. Second is the Food is Medicine (FIM) approach, an umbrella term for programs and services that link nutrition and health through the provision of food (e.g., tailored meals, produce prescriptions) and access to healthcare services. This article outlines how interventions and programs using FIM can synergize with precision nutrition approaches to make individual- or population-level tailored nutrition accessible and affordable, help to reduce the risk of metabolic diseases, and improve quality of life.

Malnutrition continues to be a major threat to health, particularly maternal and child health in low resource settings, resulting in impairments in cognitive function, growth, and development, and metabolic diseases later in life. Nutritional assessment is a cornerstone of any successful nutrition intervention or program whether in the community or at the clinic. Improved computational power and advances in technology may enable precision nutrition-based approaches for maternal and child health, which can complement current methods for nutritional assessment to identify clinical, biochemical, microbiome-related, social, and environmental characteristics to predict responses to nutritional interventions or programs. Precision nutrition has the potential to complement program monitoring, efficacy evaluation, and ultimately to inform design of interventions to improve maternal and child health.

BACKGROUND AND AIMS:In clinical populations, vitamin B12 deficiency has been associated with adverse metabolic health (e.g., gestational diabetes). Population-level data among women of reproductive age could inform screening and interventions. The objective of this analysis was to examine the prevalence of adverse metabolic characteristics (elevated adiposity and central adiposity, hypertension, elevated glycated hemoglobin [HbA1c]) and associations of vitamin B12 status with metabolic characteristics in women as part of a population-based biomarker survey in Southern India. METHODS:Participants (n = 980 women 15-40 y; not pregnant or lactating) were assessed for total vitamin B12, holotranscobalamin, methylmalonic acid, homocysteine, and HbA1c. Categorical anthropometry assessments and bioelectrical impedance analysis (e.g., whole body (WF%) and trunk (TF%) fat) were assessed among adults (≥18 y). Linear and binomial regressions were used to examine associations of vitamin B12 status with metabolic characteristics. RESULTS:Overall, 25 % of participants had HbA1c ≥5.7 % (HbA1c ≥5.7-<6.5 %: 20.0 %; ≥6.5 %: 5.0 %), and 18.6 % had hypertension (Stage 1: 16.4 %; Stage 2: 2.2 %). Among adults, 23.4 % had body mass index of (BMI) 25.0-<30.0 kg/m2, 9.6 % had BMI ≥30.0 kg/m2, 13.4 % had elevated waist circumference (WC; >88.9 cm), and 20.8 % had elevated waist-hip ratio (WHR; ≥0.85 cm). Overall, higher vitamin B12 concentrations were associated with lower BMI and WC. Among adults, higher vitamin B12 concentrations were associated with lower WF% and TF%; and lower prevalence of overweight (BMI ≥25.0 kg/m2) and elevated WC, WHR, and WF%. Similarly, vitamin B12 <148 pmol/L was associated with higher BMI and WC overall and, among adults, higher WF% and TF%, and increased overweight (BMI ≥25.0 kg/m2; prevalence ratio: 1.31; 95 % confidence interval: 1.09-1.58), and elevated WC (>88.9 cm; 1.85 [1.32-2.60]), WHR (≥85.0; 1.38 [1.07-1.78]), WF% (>35 %; 1.29 [1.10-1.51]), and TF% (>35 %; 1.25 [1.06-1.49]). CONCLUSIONS:The burden of adverse metabolic characteristics was substantial in this population of young, apparently healthy women. Among those with vitamin B12 <148 pmol/L there was increased central adiposity and overweight status. Evaluating vitamin B12 and metabolic outcomes prospectively could inform screening and interventions to improve women's health. REGISTRATION NUMBER:NCT04048330.

Malnutrition is the most common acquired cause of immunodeficiency worldwide. Nutritional deficiencies can blunt both the innate and adaptive immune response to pathogens. Furthermore, malnutrition is both a cause and consequence of infectious diseases. The bidirectional relationship between infectious diseases and undernutrition, as well as the inflammatory milieu of infectious diseases, can complicate nutritional assessment. This article aims to provide clinicians and researchers with an overview of commonly used tools to assess nutritional status, with a particular emphasis on their use in the context of infectious diseases. These tools include anthropometric, biochemical, clinical/physical, and dietary assessments to screen and evaluate undernutrition, diet quality, and food insecurity effectively.

Precision nutrition (PN) considers multiple individual-level and environmental characteristics or variables to better inform dietary strategies and interventions for optimizing health, including managing obesity and metabolic disorders. Here, we review the evidence on potential mechanisms-including ones to identify individuals most likely to respond-that can be leveraged in the development of PN interventions addressing obesity. We conducted a review of the literature and included laboratory, animal, and human studies evaluating biochemical and genetic data, completed and ongoing clinical trials, and public programs in this review. Our analysis describes the potential mechanisms related to 6 domains including genetic predisposition, circadian rhythms, physical activity and sedentary behavior, metabolomics, the gut microbiome, and behavioral and socioeconomic characteristics, i.e., the factors that can be leveraged to design PN-based interventions to prevent and treat obesity-related outcomes such as weight loss or metabolic health as laid out by the NIH 2030 Strategic Plan for Nutrition Research. For example, single nucleotide polymorphisms can modify responses to certain dietary interventions, and epigenetic modulation of obesity risk via physical activity patterns and macronutrient intake have also been demonstrated. Additionally, we identified limitations including questions of equitable implementation across a limited number of clinical trials. These include the limited ability of current PN interventions to address systemic influences such as supply chains and food distribution, healthcare systems, racial or cultural inequities, and economic disparities, particularly when designing and implementing PN interventions in low- and middle-income communities. PN has the potential to help manage obesity by addressing intra- and inter-individual variation as well as context, as opposed to "one-size fits all" approaches though there is limited clinical trial evidence to date.

Tuberculosis (TB) is the leading infectious killer worldwide, with 10.6 million cases and 1.6 million deaths in 2021 alone. One in 5 incident TB cases were attributable to malnutrition, more than double the fraction attributed to HIV. Like HIV, malnutrition is a cause of secondary immunodeficiency and has even been dubbed nutritionally acquired immunodeficiency syndrome (N-AIDS). However, malnutrition remains the neglected cousin of HIV in global TB elimination efforts. Malnutrition increases the risk for TB progression, increases disease severity, and worsens TB treatment outcomes. Thus, it is both a TB determinant and comorbidity. In this perspective, we discuss decades of data to make the case that N-AIDS, just like HIV/AIDS, also deserves special consideration in the TB elimination discourse. Fortunately, malnutrition is a modifiable risk factor and there is now empirical evidence that addressing nutrition can help us curb the TB pandemic. Recognizing malnutrition as a key determinant and comorbidity is key to detecting and treating the missing millions while also preventing additional millions from suffering TB disease.

BACKGROUND:Double-fortified salt (DFS; iron, iodine) improved iron status in randomized trials and was incorporated into India's social safety net programs, suggesting opportunities to address other micronutrient deficiencies. OBJECTIVES:To evaluate the acceptability of quadruple-fortified salt (QFS; iron, iodine, folic acid, and vitamin B12) in women and their households, using a randomized crossover trial design and triangle tests. METHODS:Women 18-49 y (n = 77) and their households were randomly assigned to receive QFS or DFS in a randomized crossover design over a 3-wk period (week 1: QFS/DFS, week 2: iodized salt, week 3: DFS/QFS). Each week, participants completed a 9-point hedonic questionnaire (1 = dislike extremely to 9 = like extremely) to evaluate 5 sensory domains (color, odor, taste, texture, and overall acceptability) of the intervention, and the remaining salt was weighed using a digital scale. Triangle tests were conducted among women to evaluate sensory discrimination of salt consumed in rice dishes prepared using standardized recipes. Mixed models were used to examine hedonic ratings and salt use; salt type, sequence, and period were included as fixed effects, and household was included as a random effect. Binomial tests were used to evaluate sensory discrimination of salt type in triangle tests. RESULTS:Mean hedonic ratings for most of the 5 sensory domains were ≥7 (like moderately) and did not differ by salt type [overall acceptability mean (SD): QFS: 7.8 (0.7) compared with DFS: 7.7 (1.2); P = 0.68]. Household salt use (weighed) did not differ by salt type. During the 3-wk intervention period, weighed salt use and hedonic ratings significantly increased, indicating a period effect independent of salt type or sequence. In triangle tests, rice samples prepared with QFS, DFS, or iodized salt were not distinguishable. CONCLUSIONS:Acceptability of QFS was high, based on individual hedonic ratings and weighed household salt use. Rice dishes prepared with DFS, QFS, and iodized salt were not distinguishable. Findings informed the design of a randomized trial of QFS in this population. This trial was registered at clinicaltrials.gov as NCT03853304 and CTRI/2024/04/066208.

Background Vitamin B-12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B-12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. Objectives To evaluate the benefits and harms of oral vitamin B-12 supplementation during pregnancy on maternal and child health outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. Selection criteria Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B-12 supplementation compared to placebo or no vitamin B-12 supplementation during pregnancy. Data collection and analysis We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. Main results The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B-12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B-12 supplementation varied from 5 mu g/day to 250 mu g/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B-12 supplementation compared to placebo or no vitamin B-12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B-12 status: vitamin B-12 supplementation during pregnancy may reduce the risk of maternal vitamin B-12 deficiency compared to placebo or no vitamin B-12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B-12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B-12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I-2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B-12 supplementation during pregnancy on neural tube defects. Infant vitamin B-12 status: children born to women who received vitamin B-12 supplementation had higher total vitamin B-12 concentrations compared to placebo or no vitamin B-12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B-12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B-12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). Authors' conclusions Oral vitamin B-12 supplementation during pregnancy may reduce the risk of maternal vitamin B-12 deficiency and may improve maternal vitamin B-12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B-12 supplementation, but the evidence is very uncertain. The effects of vitamin B-12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B-12 supplementation during pregnancy may improve maternal and infant vitamin B-12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

BACKGROUND:Limited information on the co-prevalence of undernutrition, micronutrient deficiencies, overnutrition, and abnormal levels of noncommunicable disease biomarkers at the same time in children and adolescents in India hinders efforts to comprehensively address their health. OBJECTIVES:This study aimed to examine the prevalence and correlates of double burden of malnutrition (DBM) and triple burden of malnutrition (TBM) among children and adolescents (5-19 y) to inform policies and programs. METHODS:A total of 17,599 children (5-9 y) and 16,184 adolescents (10-19 y) with available biomarker data from the Comprehensive National Nutrition Survey were included. Malnutrition was defined based on either undernutrition based on anthropometry, overnutrition/abnormal metabolic markers, and anemia/micronutrient deficiency. DBM was defined as the coexistence of any 2 forms of malnutrition. DBM+ was defined as the coexistence of undernutrition and/or micronutrient deficiency along with overnutrition. TBM was defined as having the coexistence of all 3 forms of malnutrition. The prevalence of DBM, DBM+, and TBM was estimated accounting for probabilistic selection. We used mixed-effect binomial regression to determine correlates of DBM/TBM in children and adolescents separately. RESULTS:The prevalence of DBM, DBM+, and TBM was 50.8%, 37.2%, and 14.4%, respectively, in children and 53.4%, 36.1%, and 12.7%, respectively, in adolescents. The prevalence of DBM+ was significantly higher in girls compared to in boys in the 5-9 y age group. In children, being in a disadvantaged caste group, having a lower wealth index, having inadequate diet diversity, having no maternal schooling, and having a recent history of acute illness were associated with DBM. In adolescents, being in a disadvantaged caste group, maternal occupation, and lower paternal age were correlated with DBM. A similar set of variables was associated with TBM in both age groups. CONCLUSIONS:The prevalence of DBM and TBM is substantial in children and adolescents in India and varies across states. Socioeconomic factors and acute illness were the main correlates for DBM and TBM.

BACKGROUND:Iron and folic acid supplementation have been recommended in pregnancy for anaemia prevention, and may improve other maternal, pregnancy, and infant outcomes. OBJECTIVES:To examine the effects of daily oral iron supplementation during pregnancy, either alone or in combination with folic acid or with other vitamins and minerals, as an intervention in antenatal care. SEARCH METHODS:We searched the Cochrane Pregnancy and Childbirth Trials Registry on 18 January 2024 (including CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, conference proceedings), and searched reference lists of retrieved studies. SELECTION CRITERIA:Randomised or quasi-randomised trials that evaluated the effects of oral supplementation with daily iron, iron + folic acid, or iron + other vitamins and minerals during pregnancy were included. DATA COLLECTION AND ANALYSIS:Review authors independently assessed trial eligibility, ascertained trustworthiness based on pre-defined criteria, assessed risk of bias, extracted data, and conducted checks for accuracy. We used the GRADE approach to assess the certainty of the evidence for primary outcomes. We anticipated high heterogeneity amongst trials; we pooled trial results using a random-effects model (average treatment effect). MAIN RESULTS:We included 57 trials involving 48,971 women. A total of 40 trials compared the effects of daily oral supplements with iron to placebo or no iron; eight trials evaluated the effects of iron + folic acid compared to placebo or no iron + folic acid. Iron supplementation compared to placebo or no iron Maternal outcomes: Iron supplementation during pregnancy may reduce maternal anaemia (4.0% versus 7.4%; risk ratio (RR) 0.30, 95% confidence interval (CI) 0.20 to 0.47; 14 trials, 13,543 women; low-certainty evidence) and iron deficiency at term (44.0% versus 66.0%; RR 0.51, 95% CI 0.38 to 0.68; 8 trials, 2873 women; low-certainty evidence), and probably reduces maternal iron-deficiency anaemia at term (5.0% versus 18.4%; RR 0.41, 95% CI 0.26 to 0.63; 7 trials, 2704 women; moderate-certainty evidence), compared to placebo or no iron supplementation. There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence). The evidence is very uncertain for adverse effects (21.6% versus 18.0%; RR 1.29, 95% CI 0.83 to 2.02; 12 trials, 2423 women; very low-certainty evidence) and severe anaemia (Hb < 70 g/L) in the second/third trimester (< 1% versus 3.6%; RR 0.22, 95% CI 0.01 to 3.20; 8 trials, 1398 women; very low-certainty evidence). No trials reported clinical malaria or infection during pregnancy. Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation. However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence). There is probably little to no difference in preterm birth (7.6% versus 8.2%; RR 0.93, 95% CI 0.84 to 1.02; 11 trials, 18,827 infants; moderate-certainty evidence) and there may be little to no difference in neonatal death (1.4% versus 1.5%, RR 0.98, 95% CI 0.77 to 1.24; 4 trials, 17,243 infants; low-certainty evidence) or congenital anomalies, including neural tube defects (41 versus 48 events; RR 0.88, 95% CI 0.58 to 1.33; 4 trials, 14,377 infants; low-certainty evidence). Iron + folic supplementation compared to placebo or no iron + folic acid Maternal outcomes: Daily oral supplementation with iron + folic acid probably reduces maternal anaemia at term (12.1% versus 25.5%; RR 0.44, 95% CI 0.30 to 0.64; 4 trials, 1962 women; moderate-certainty evidence), and may reduce maternal iron deficiency at term (3.6% versus 15%; RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low-certainty evidence), compared to placebo or no iron + folic acid. The evidence is very uncertain about the effects of iron + folic acid on maternal iron-deficiency anaemia (10.8% versus 25%; RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; very low-certainty evidence), or maternal deaths (no events; 1 trial; very low-certainty evidence). The evidence is uncertain for adverse effects (21.0% versus 0.0%; RR 44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; low-certainty evidence), and the evidence is very uncertain for severe anaemia in the second or third trimester (< 1% versus 5.6%; RR 0.12, 95% CI 0.02 to 0.63; 4 trials, 506 women; very low-certainty evidence), compared to placebo or no iron + folic acid. Infant outcomes: There may be little to no difference in infant low birthweight (33.4% versus 40.2%; RR 1.07, 95% CI 0.31 to 3.74; 2 trials, 1311 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. Infants born to women who received iron + folic acid during pregnancy probably had higher birthweight (MD 57.73 g, 95% CI 7.66 to 107.79; 2 trials, 1365 infants; moderate-certainty evidence), compared to placebo or no iron + folic acid. There may be little to no difference in other infant outcomes, including preterm birth (19.4% versus 19.2%; RR 1.55, 95% CI 0.40 to 6.00; 3 trials, 1497 infants; low-certainty evidence), neonatal death (3.4% versus 4.2%; RR 0.81, 95% CI 0.51 to 1.30; 1 trial, 1793 infants; low-certainty evidence), or congenital anomalies (1.7% versus 2.4; RR 0.70, 95% CI 0.35 to 1.40; 1 trial, 1652 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. A total of 19 trials were conducted in malaria-endemic countries, or in settings with some malaria risk. No studies reported maternal clinical malaria; one study reported data on placental malaria. AUTHORS' CONCLUSIONS:Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term. For other maternal and infant outcomes, there was little to no difference between groups or the evidence was uncertain. Future research is needed to examine the effects of iron supplementation on other maternal and infant health outcomes, including infant iron status, growth, and development.

Background: RBC folate concentrations are monitored at the population level, with a recommended threshold for optimal neural tube defect (NTD) prevention. A corresponding threshold for serum folate has not been established.Objectives: This study aimed to estimate the serum folate insufficiency threshold corresponding to the RBC folate threshold for NTD prevention and examine how this threshold is modified by vitamin B12 status.Methods: Participants were women (15-40 y; not pregnant or lactating; n = 977) from a population-based biomarker survey in Southern India. RBC folate and serum folate were measured via microbiologic assay. RBC folate deficiency (<305 nmol/L) and insufficiency (<748 nmol/L), serum vitamin B12 deficiency (<148 pmol/L) and vitamin B12 insufficiency (<221 pmol/L), elevated plasma MMA (>0.26 mu mol/L), elevated plasma homocysteine (>10.0 mu mol/L), and elevated HbA1c (>= 6.5%) were evaluated. Bayesian linear models were used to estimate unadjusted and adjusted thresholds.Results: Compared with adequate vitamin B12 status, the estimated serum folate threshold was higher in participants with serum vitamin B12 deficiency (72.5 vs. 28.1 nmol/L) or vitamin B12 insufficiency (48.7 vs. 24.3 nmol/L) and elevated MMA (55.6 vs. 25.9 nmol/L). The threshold was lower in participants with elevated HbA1c (HbA1c >= 6.5% vs. <6.5%; 21.0 vs. 40.5 nmol/L).Conclusions: The estimated serum folate threshold for optimal NTD prevention was similar to previous reports (24.3 vs. 25.6 nmol/L) among participants with sufficient vitamin B12 status. However, this threshold was more than 2-fold higher in participants with vitamin B12 deficiency and substantially higher across all indicators of insufficient vitamin B12 status (<221 pmol/L, elevated MMA, combined B12, impaired vitamin B12 status), and lower in participants with elevated HbA1c. Findings suggest a serum folate threshold for NTD prevention may be possible in some settings; however, it may not be appropriate in populations with high prevalence of vitamin B12 insufficiency. Am J Clin Nutr 2023;xx:xx-xx.This trial was registered at https://clinicaltrials.gov as NCT04048330.