Multi-micronutrient Intervention Research Articles

Efficacy of Macro and Micronutrient Interventions in Adolescent Nutritional Status: A Systematic Review

The authors conducted a systematic review of adolescents receiving a macronutrient (iron, zinc) intervention compared to a multi-micronutrient intervention to investigate their efficacy on nutritional status. Systematic searches were conducted in four database sources—Science Direct, ProQuest, EBSCO, and Google Scholar. A PICO worksheet was used to define keywords, including 1) Patient/Problem: Preconception for adolescent OR girl student, 2) Intervention: Iron and zinc OR Fe and Zn OR macronutrients, 3) Comparison: Multi-micronutrient, and 4) Outcome: Nutritional status. Inclusion criteria included female adolescents aged 9–24 years and English and Indonesian articles published from 2013 to 2020. The risk of bias was assessed by minimizing four potential sources of bias: sample selection, research design, control of confounding variables, and data collection techniques. Result: 10 relevant studies discussing iron, zinc, and multi-micronutrient supplements for adolescents were identified. Iron and zinc interventions are efficacious in preventing anemia, enhancing hemoglobin concentration, improving body mass index, and reducing the risk of low birth weight and preeclampsia for women in the preconception phase. The multi-micronutrient intervention has similar efficacy, but it can better affect the maternal immune response and the production of the human placental lactogen hormone, which ultimately increases placental weight and birth weight while lowering the risk of abortion and prematurity. Conclusion: Iron, zinc, and multi-micronutrient interventions play a pivotal role in improving the nutritional status of adolescents in preparing the preconception phase because they provide positive benefits and can prevent nutritional deficiencies before pregnancy, during pregnancy, and after delivery.

Evaluation of a Physical Activity and Multi-Micronutrient Intervention on Cognitive and Academic Performance in South African Primary Schoolchildren.

Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1%), Mage (mean age) = 8.42 ± 1.94 years) completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group × time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance.

Feasibility and Effectiveness of a Multi-Micronutrient Intervention as a Palliative Care Therapy in Patients With Congestive Heart Failure

ObjectivesVeterans with HF are at risk of micronutrient depletion due to combined systemic disease and drug induced altered nutrient disposition. This pilot aimed to test feasibility and effectiveness of a MMI to improve micronutrient status, cardiac function and quality of life in Veterans with HF. MethodsA pre/post repeated measures design was used. Veterans with stable HF stage B-D, left ventricular ejection fraction (LVEF) ≤45%, from ischemic cardiomyopathy with systolic dysfunction were recruited. The 6-month MMI was 3 tabs daily providing thiamin (B1) 100 mg, 50 mg each of riboflavin, niacin, pantothenic acid, pyridoxine (B6), inositol, 25 mg phosphatidyl choline, 400 mcg folic acid, and 50 mcg each of B12 and biotin, and 50 mg elemental zinc (Zn). Ergocalciferol was given as 50,000 IU weekly for 2 months then every 2 weeks for 4 months. Micronutrient status and LVEF (echocardiogram) were determined as least-squares mean (± standard error, SE) estimated from general linear mixed effect models fitted to micronutrient measurements adjusting for age (18–65 Vs. > 65); feasibility of MMI assessed as % consumed. ResultsThis abstract focuses on the nutrient status at baseline, feasibility of the MMI, and change in nutrient status following MMI. Twenty-two male Veterans (86% Caucasian), median 64 years (59–75 interquartile range, IQR) started MMI; 20 completed. At baseline, median (IQR) dietary intake was 1639 (1472–1838) calories, 36 (28–41) % fat, 13 (10–15) % saturated fat, 2981 (2067–3534) mg sodium while following the American Heart Association diet with 2 gm sodium restriction. Micronutrient intake was 1.2 (0.9–1.4) mg B1, 1.2 (1.0–1.8) mg B6, 49 (38–166) IU Vitamin D, and 7 (5–10) mg zinc. Median % compliance with MMI at 3 and 6 months was ≥ 92 and ≥94, respectively. Baseline and changes in blood measures of micronutrients were: B1, 119 (SE 13) and 96 (SE 20, p< 0.0001) nmol/L; B6, 11.4 (SE 6.3) and 57.3 (SE 9.2, p< 0.0001) ng/mL; total 25-OH Vitamin D, 31.2 (SE 2.3) and 6.5 (SE 3.4, p = 0.057) ng/mL; Zn, 81.4 (SE 5.1) and 13.8 (7.6, p = 0.07) mcg/dL. LVEF at baseline and 6 months were 28.9 (SE 1.6) % and 30.0 (SE 1.7) %, respectively (p = 0.64). ConclusionsThe feasibility of adding MMI to complex pharmaceutical regimens in male Veterans with stable HF was high. MMI was effective in improving micronutrient status and preserved LVEF. Funding SourcesDepartment of Veterans Affairs

Association of nutritional status and anemia with multi-micronutrient supplementation in young children in Peru

Introduction:Although several social interventions have been developed by the Peruvian State, anemia is present in one out of every two children in Peru. Thus, it is important to evaluate whether such interventions are achieving their objectives.Objective:This study aimed to determine the association of nutritional status and anemia with multi-micronutrient supplementation in children younger than three years in Huancayo, Peru.Materials and Methods:This retrospective, longitudinal, analytical, and observational study included secondary data of children younger than 3 years from the Sicaya District, in the Huancayo province. Data were collected from health center medical records. Nutritional and anemia status, and socio-demographic characteristics of children receiving multi-micronutrient supplementation were recorded. Statistical analyses were based on generalized linear models.Results:Data of 76 children with available medical records were analyzed, and their pre- and post-intervention median ages were 6 and 11 months (range: 7–35 months), respectively. Significant positive linear correlations were observed between the number of multi-micronutrient doses and weight, height, and hemoglobin concentration. In bivariate and multivariate analyses, no significant associations were observed between anthropometric measurements and anemia (after multi-micronutrient intervention) (p>0.05), nor between the number of received doses of multi-micronutrients, sex, and age.Conclusion:Multi-micronutrient supplementation may be correlated with both physiological and anthropometric variables, but not with indicators of child development. These associations require further evaluations to determine whether social programs promoting multi-micronutrient supplementation improve the development of children with anemia.

Impact of multi-micronutrient supplementation on lipidemia of children and adolescents

Micronutrient supplementation has been extensively explored as a strategy to improve health and reduce risk of chronic diseases. Fat-soluble vitamins like A and E with their antioxidant properties and mechanistic interactions with lipoproteins, have potentially a key impact on lipid metabolism and lipidemia. The impact of micronutrients on lipid metabolism requires further investigation including characterization of plasma lipidome following supplementation and any cause-effect on circulating lipids. In this study, we elucidate the effect and associations of a multi-micronutrient intervention in Brazilian children and teens with lipoprotein alterations and lipid metabolism. Our analysis suggests a combination of short and long-term impact of supplementation on lipid metabolism, potentially mediated primarily by α-tocopherol (vitamin E) and retinol (vitamin A). Among the lipid classes, levels of phospholipids, lysophospholipids, and cholesterol esters were impacted the most along with differential incorporation of stearic, palmitic, oleic and arachidonic acids. Integrated analysis with proteomic data suggested potential links to supplementation-mediated alterations in protein levels of phospholipases and pyruvate dehydrogenase kinase 1 (PDK1). Associations between the observed differences in lipidemia, total triglyceride, and VLDL-cholesterol levels suggest that micronutrients may play a role in reducing these risk factors for cardiovascular disease in children. This would require further investigation.

Pregnant Women in Four Low-Middle Income Countries Have a High Prevalence of Inadequate Dietary Intakes That Are Improved by Dietary Diversity.

Background: Up-to-date dietary data are required to understand the diverse nutritional challenges of pregnant women living in low-middle income countries (LMIC). To that end, dietary data were collected from 1st trimester pregnant women in rural areas of Guatemala, India, Pakistan, and Democratic Republic of the Congo (DRC) participating in a maternal lipid-based nutrient supplement (LNS) Randomized Controlled Trial to examine dietary diversity (DD), usual group energy and nutrient intakes, and prevalence of inadequate dietary intakes. Methods: Two 24-h dietary recalls were conducted in ~240 pregnant women/site (total n = 966) prior to 12-week gestation. Adequate DD was assessed, i.e., ≥5 major food groups consumed within the past 24 h. Median, Q1, Q3 intakes (without LNS) of energy, macronutrients, 12 micronutrients, and phytate were examined. The “at risk” prevalence of inadequate intakes were based on international guidelines for pregnant women. Results: Dietary patterns varied widely among sites, with adequate DD reported: 20% (Pakistan), 25% (DRC), 50% (Guatemala), and 70% (India). Significantly higher intakes of most key nutrients were observed in participants with adequate DD. More than 80% of women in all sites had inadequate intakes of folate, vitamin B12, and choline, and >80% of women in India and DRC also had inadequate intakes of calcium, thiamine, riboflavin, and vitamin B6. Conclusions: Our data highlight the likely need for micronutrient supplementation in pregnancy, specifically multi-micronutrient interventions, and support the value of increasing DD as part of sustainable long-term nutrition programs for women of reproductive age in these poor rural settings in LMIC.

Clinical and Vitamin Response to a Short-Term Multi-Micronutrient Intervention in Brazilian Children and Teens: From Population Data to Interindividual Responses.

ScopeMicronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals.Methods and resultsA 6‐week multivitamin/mineral intervention is conducted in 9–13 year olds. Participants (136) are (i) their own control (n‐of‐1); (ii) monitored for compliance; (iii) measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food intake parameters at baseline, post intervention, and following a 6‐week washout; and (iv) had their ancestry accounted for as modifier of vitamin baseline or response. The same intervention is repeated the following year (135 participants). Most vitamins respond positively and many clinical parameters change in directions consistent with improved metabolic health to the intervention. Baseline levels of any metabolite predict its own response to the intervention. Elastic net penalized regression models are identified, and significantly predict response to intervention on the basis of multiple vitamin/clinical baseline measures.ConclusionsThe study design, computational methods, and results are a step toward developing recommendations for optimizing vitamin levels and health parameters for individuals.

Helminth infections and micronutrients in school-age children: a systematic review and meta-analysis

Helminth infections and micronutrient deficiencies are highly prevalent in developing countries. Neither condition typically causes overt disease, but they do lead to indirect morbidity such as impaired physical and cognitive development. We aimed to systematically review current evidence on the relation of helminth infections with micronutrient status in school-age children worldwide. We included both observational studies and randomized controlled trials (RCTs). We applied a random-effects meta-analysis to estimate 1) cross-sectional associations between helminths and micronutrient status, 2) effects of anthelminthic treatment on micronutrient status, and 3) effects of micronutrient supplementation on helminth infection and reinfection. Meta-analyses of observational studies showed an association between helminth infections and serum retinol [standardized mean difference (SMD): -0.30; 95% CI: -0.48, -0.13] but not serum ferritin (SMD: 0.00; 95% CI: -0.7, 0.7). Conversely, meta-analyses of anthelminthic treatment RCTs showed a positive effect on ferritin (SMD: 0.16; 95% CI: 0.09, 0.22) but not retinol (SMD: 0.04; 95% CI: -0.06, 0.14). The number of studies on micronutrients other than ferritin and retinol was not sufficient for pooling. Meta-analyses of micronutrient-supplementation RCTs showed only a modest protective effect for multimicronutrient interventions on helminth infection and reinfection rates (OR: 0.77; 95% CI: 0.61, 0.97). In this review, we show evidence of distinct associations between helminth infections and micronutrients in school-age children. More studies are needed on micronutrients other than iron and vitamin A and on possible helminth species-specific effects. A thorough comprehension of the interplay between helminth infections and micronutrients will help guide integrated and sustainable intervention strategies in affected children worldwide.

Assessing the Impact of Micronutrient Intervention Programs Implemented under Special Circumstances—Meeting Report

The World Food Programme and the Office of the United Nations High Commissioner for Refugees organized a meeting of experts to discuss evaluation of micronutrient interventions under special circumstances, such as emergency and refugee situations. Multimicronutrient interventions for groups with higher needs may include home fortification products for young children or supplements for pregnant and lactating women. The choice of preparation should be guided by target group needs, evidence of efficacy of a product or its compounds, acceptability, and cost-effectiveness. Different designs can be used to assess whether an intervention has the desired impact. First, program implementation and adherence must be ascertained. Then, impact on micronutrient status can be assessed, but design options are often limited by logistic challenges, available budget, security issues, and ethical and practical issues regarding nonintervention or placebo groups. Under these conditions, a plausibility design using pre- and postintervention cross-sectional surveys, a prospective cohort study, or a step-wedge design, which enrolls groups as they start receiving the intervention, should be considered. Post hoc comparison of groups with different adherence levels may also be useful. Hemoglobin is often selected as an impact indicator because it is easily measured and tends to respond to change in micronutrient status, especially iron. However, it is not a very specific indicator of micronutrient status, because it is also influenced by inflammation, parasitic infestation, physiological status (age, pregnancy), altitude, and disorders such as thalassemia and sickle cell disease. Given the constraints described above, replicability of impact in different contexts is key to the validation of micronutrient interventions.

Multiple micronutrient deficiencies persist during early childhood in Mongolia.

Data on the prevalence of micronutrient deficiencies in children in Mongolia is limited. We therefore determined the prevalence of anaemia, iron deficiency anaemia (IDA), and deficiencies of iron, folate, vitamin A, zinc, selenium, and vitamin D among young Mongolian children. Anthropometry and non-fasting morning blood samples were collected from 243 children aged 6-36 months from 4 districts in Ulaanbaatar and 4 rural capitols for haemoglobin (Hb), serum ferritin, folate, retinol, zinc, selenium, and 25-hydroxyvitamin D (25-OHD) assays. Children with alpha-1-glycoprotein >1.2mg/L (n=27) indicative of chronic infection were excluded, except for folate, selenium, and 25-hydroxyvitamin D assays. Of the children 14.5% were stunted and none were wasted. Zn deficiency (serum Zn <9.9 micromol/L) had the highest prevalence (74%), followed by vitamin D deficiency 61% (serum 25-OHD<25 nmol/L). The prevalence of anaemia (24%) and iron deficiency anaemia (IDA) (16%) was lower, with the oldest children (24-36 mos) at lowest risk. Twenty one percent of the children had low iron stores, and 33% had vitamin A deficiencies (serum retinol < 0.70 micromol/L), even though two thirds had received vitamin A supplements. Serum selenium values were low, perhaps associated with low soil selenium concentrations. In contrast, no children in Ulaanbaatar and only 4% in the provincial capitols had low serum folate values (<6.8 nmol/L). Regional differences (p<0.05) existed for anaemia, deficiencies of vitamin A, folate, and selenium, but not for zinc or IDA. Of the children, 78% were at risk of > or = two coexisting micronutrient deficiencies emphasizing the need for multimicronutrient interventions in Mongolia.

Multiple micronutrient deficiencies persist during early childhood in Mongolia

The effectiveness of interventions in Mongolia to combat micronutrient deficiencies in children is uncertain. We determined the prevalence of anemia, iron deficiency anemia (IDA), and deficiencies of Fe, Zn, Se, and vitamin A among young Mongolian children. Anthropometry and non‐fasting morning blood samples were collected from 243 children (126 M, 117 F) aged 6–36 months from Ulaanbaatar and 4 rural capitals for hemoglobin (Hb), serum (s) ferritin, Zn, Se, and retinol assays. Children with α‐1‐glycoprotein&gt;1.2 mg/L (n = 27) indicative of infection were excluded. Of the children 14.5% were stunted and none were wasted. Zn deficiency (sZn&lt;9.9μmol/L) had the highest prevalence (74%). The prevalence of anemia (24%) and iron deficiency anemia (IDA) (16%) were lower, with the oldest children (24–36 mos) at lowest risk. 21% of the children had Fe deficiency, and 33% had vitamin A (sretinol &lt;0.70 μmol/L) deficiency. Serum Se values were low, as noted for South Island NZ children, where soil Se is low. Regional differences (p&lt;0.05) existed for anemia, deficiencies of Se and vitamin A, but not Zn or IDA. Age, location, log serum ferritin, infection, and serum zinc were major predictors of hemoglobin. Of the children, 64% were at risk of two or more coexisting micronutrient deficiencies emphasizing the need for multimicronutrient interventions in Mongolia. Funded by WHO, UNICEF, World Vision Mongolia, University of Otago.

We Know Much about What to Do but Little about How to Do it: Experiences with a Weekly Multimicronutrient Supplementation Campaign

Global population growth is concentrated in urban areas, but there is little understanding of how to implement the necessary interventions to control food and nutrition insecurity. In the urban area of Peru, food insecurity is characterized mainly by micronutrient deficiencies and not by energy deficiency. To increase the effectiveness and cost-effectiveness of weekly multimicronutrient supplementation programs in poor urban communities. A series of operational studies were conducted of preventive weekly multimicronutrient supplementation to reduce micronutrient-deficiency anemia in a population consisting of 8,081 children under 5 years of age and 20,082 women and adolescent girls of reproductive age (12 through 44 years). This is one of a series of papers that describe in as much detail as possible the experiences of a multimicronutrient intervention program for poor urban mothers and their young children and summarizes the lessons learned for consideration of future programming. This paper shows that such programs can achieve a high compliance with good training of program staff involvement of the community, education and motivation of beneficiaries, adequate supplies, and careful monitoring.

Risk of zinc, iodine and other micronutrient deficiencies among school children in North East Thailand

Micronutrient deficiencies during childhood can contribute to impairments in growth, immune competence, and mental and physical development, and the coexistence of several such deficiencies can adversely affect the efficacy of single micronutrient interventions. To assess the prevalence of zinc and iodine deficiency and their interrelationships with vitamin A deficiency and anemia and associations with socio-economic status, hemoglobin type, and anthropometry in a cross-sectional study. A total of 10 primary schools in North East Thailand. Non-fasting venipuncture blood samples and casual urine samples were collected from 567 children aged 6-13 years. Anthropometric measures and serum zinc, albumin, C-reactive protein and urinary iodine, are reported here and integrated with published data on vitamin A, anemia, and socio-economic status. Of the children, 57% had low serum zinc and 83% had urinary iodine levels below the 100 microg/l cutoff. Suboptimal serum zinc and urinary iodine concentrations may result from low intakes of zinc and iodized salt. Significant risk factors for low serum zinc were serum retinol <1.05 micromol/l and being male. Those for urinary iodine <100 microg/l were height-for-age score>median and being female. For serum retinol <1.05 micromol/l, risk factors were low hemoglobin, low serum zinc, and <9 years, and for low hemoglobin indicative of anemia risk factors were <9 years, AE hemoglobinopathy, and serum retinol <1.05 micromol/l. Of the children, 60% were at risk of two or more coexisting micronutrient deficiencies, most commonly suboptimal urinary iodine and low serum zinc. The findings emphasize the need for multimicronutrient interventions in North East Thailand.

Multimicronutrient Interventions but Not Vitamin A or Iron Interventions Alone Improve Child Growth: Results of 3 Meta-Analyses

Meta-analyses of randomized controlled intervention trials were conducted to assess the effects of vitamin A, iron, and multimicronutrient interventions on the growth of children < 18 y old. A PubMed database search and other methods identified 14 vitamin A, 21 iron, and 5 multimicronutrient intervention studies that met the design criteria. Weighted mean effect sizes and CI were calculated using a random effects model for changes in height and weight. Tests for homogeneity and stratified analyses by predefined characteristics were conducted. Vitamin A interventions had no significant effect on growth; effect sizes were 0.08 (95% CI: -0.20, 0.36) for height and -0.01 (95% CI: -0.24, 0.22) for weight. Iron interventions also had no significant effect on child growth. Overall effect sizes were 0.09 (95% CI: -0.07, 0.24) for height and 0.13 (95% CI: -0.05, 0.30) for weight. The results were similar across categories of age, duration of intervention, mode and dosage of intervention, and baseline anthropometric status. Iron interventions did result in a significant increase in hemoglobin (Hb) concentrations with an effect size of 1.49 (95% CI: 0.46, 2.51). Multimicronutrient interventions had a positive effect on child growth; the effect sizes were 0.28 (95% CI: 0.16, 0.41) for height and 0.28 (95% CI: -0.07, 0.63) for weight. Interventions limited to only vitamin A or iron did not improve child growth. Multimicronutrient interventions, on the other hand, improved linear and possibly ponderal growth in children.

Moderate zinc and vitamin A deficiency in breast milk of mothers from East-Jakarta.

To gain information about the micronutrient status of urban, middle-income, breast-feeding mothers in relation to zinc and selected fat-soluble vitamins in plasma and breast milk and to assess possible interaction between the measured micronutrients. Cross-sectional study. 91 mothers and their infants living in middle-income areas of Jakarta, Indonesia. None of the measured anthropometric data of the mothers (e.g. BMI: 22.0+/-3.1 kg/m2) and their infants (birth weight: 3.2+/-0.5 kg) gave any indication of undernutrition. The mean concentrations in blood were 124+/-18 g/l for hemoglobin, 385+/-111 microg/l for retinol, 34+/-23 microg/l for alpha-carotene, 104+/-72 microg/l for beta-carotene, 7.7+/-3.3 mg/l for alpha-tocopherol, 0.57+/-0.23 mg/l for gamma-tocopherol, 855+/-242 microg/l for zinc, and the median concentration of lycopene was 29 microg/l. The median breast milk concentrations were 420 microg/l for retinol, 7.8 microg/l for beta-carotene, and 2.7 mg/l for zinc. With increased duration of lactation, vitamin A and zinc concentrations significantly decreased in breast milk whereas plasma zinc concentration increased. Plasma alpha- and beta-carotene were positively correlated (P < 0.0001) with each other and with plasma lycopene. Breast milk beta-carotene was positively correlated with breast milk retinol and with plasma beta-carotene (P < 0.0001). There was no correlation between zinc and vitamin A in either breast milk or plasma. Forty per cent of the mothers were anemic, 29.1% had a low plasma zinc concentration, and 23.7% had a moderately low plasma vitamin A concentration. Breast milk from 70% of the women had a low concentration of vitamin A and that from 66% had a low concentration of zinc. Multi-micronutrient intervention should be considered to provide a sufficient supply of zinc and vitamin A for growth of exclusively breast-fed infants.