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1.  The Micronutrient Genomics Project: a community-driven knowledge base for micronutrient research 
Genes & Nutrition  2010;5(4):285-296.
Micronutrients influence multiple metabolic pathways including oxidative and inflammatory processes. Optimum micronutrient supply is important for the maintenance of homeostasis in metabolism and, ultimately, for maintaining good health. With advances in systems biology and genomics technologies, it is becoming feasible to assess the activity of single and multiple micronutrients in their complete biological context. Existing research collects fragments of information, which are not stored systematically and are thus not optimally disseminated. The Micronutrient Genomics Project (MGP) was established as a community-driven project to facilitate the development of systematic capture, storage, management, analyses, and dissemination of data and knowledge generated by biological studies focused on micronutrient–genome interactions. Specifically, the MGP creates a public portal and open-source bioinformatics toolbox for all “omics” information and evaluation of micronutrient and health studies. The core of the project focuses on access to, and visualization of, genetic/genomic, transcriptomic, proteomic and metabolomic information related to micronutrients. For each micronutrient, an expert group is or will be established combining the various relevant areas (including genetics, nutrition, biochemistry, and epidemiology). Each expert group will (1) collect all available knowledge, (2) collaborate with bioinformatics teams towards constructing the pathways and biological networks, and (3) publish their findings on a regular basis. The project is coordinated in a transparent manner, regular meetings are organized and dissemination is arranged through tools, a toolbox web portal, a communications website and dedicated publications.
PMCID: PMC2989004  PMID: 21189865
Micronutrient; Bioinformatics; Database; Genomics
2.  Nutrigenomic Analysis of Diet-Gene Interactions on Functional Supplements for Weight Management 
Current Genomics  2008;9(4):239-251.
Recent advances in molecular biology combined with the wealth of information generated by the Human Genome Project have fostered the emergence of nutrigenomics, a new discipline in the field of nutritional research. Nutrigenomics may provide the strategies for the development of safe and effective dietary interventions against the obesity epidemic. According to the World Health Organization, more than 60% of the global disease burden will be attributed to chronic disorders associated with obesity by 2020. Meanwhile in the US, the prevalence of obesity has doubled in adults and tripled in children during the past three decades. In this regard, a number of natural dietary supplements and micronutrients have been studied for their potential in weight management. Among these supplements, (–)-hydroxycitric acid (HCA), a natural extract isolated from the dried fruit rind of Garcinia cambogia, and the micronutrient niacin-bound chromium(III) (NBC) have been shown to be safe and efficacious for weight loss. Utilizing cDNA microarrays, we demonstrated for the first time that HCA-supplementation altered the expression of genes involved in lipolytic and adipogenic pathways in adipocytes from obese women and up-regulated the expression of serotonin receptor gene in the abdominal fat of rats. Similarly, we showed that NBC-supplementation up-regulated the expression of myogenic genes while suppressed the expression of genes that are highly expressed in brown adipose tissue in diabetic obese mice. The potential biological mechanisms underlying the observed beneficial effects of these supplements as elucidated by the state-of-the-art nutrigenomic technologies will be systematically discussed in this review.
PMCID: PMC2682937  PMID: 19452041
Insulin resistance; glucose tolerance factor; supplemental chromium; Garcinia cambogia; (-)-hydroxycitric acid; overweight; obesity; diabetes; cardiovascular disease; nutritional interventions; microarrays; nutrigenomics.
3.  The Influence of Micronutrients in Cell Culture: A Reflection on Viability and Genomic Stability 
BioMed Research International  2013;2013:597282.
Micronutrients, including minerals and vitamins, are indispensable to DNA metabolic pathways and thus are as important for life as macronutrients. Without the proper nutrients, genomic instability compromises homeostasis, leading to chronic diseases and certain types of cancer. Cell-culture media try to mimic the in vivo environment, providing in vitro models used to infer cells' responses to different stimuli. This review summarizes and discusses studies of cell-culture supplementation with micronutrients that can increase cell viability and genomic stability, with a particular focus on previous in vitro experiments. In these studies, the cell-culture media include certain vitamins and minerals at concentrations not equal to the physiological levels. In many common culture media, the sole source of micronutrients is fetal bovine serum (FBS), which contributes to only 5–10% of the media composition. Minimal attention has been dedicated to FBS composition, micronutrients in cell cultures as a whole, or the influence of micronutrients on the viability and genetics of cultured cells. Further studies better evaluating micronutrients' roles at a molecular level and influence on the genomic stability of cells are still needed.
PMCID: PMC3678455  PMID: 23781504
4.  A Screen for Suppressors of Gross Chromosomal Rearrangements Identifies a Conserved Role for PLP in Preventing DNA Lesions 
PLoS Genetics  2007;3(8):e134.
Genome instability is a hallmark of cancer cells. One class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (GCRs). GCRs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. Here, we report the results of a genome-wide screen in Saccharomyces cerevisiae aimed at identifying novel suppressors of GCR formation. The most potent novel GCR suppressor identified is BUD16, the gene coding for yeast pyridoxal kinase (Pdxk), a key enzyme in the metabolism of pyridoxal 5′ phosphate (PLP), the biologically active form of vitamin B6. We show that Pdxk potently suppresses GCR events by curtailing the appearance of DNA lesions during the cell cycle. We also show that pharmacological inhibition of Pdxk in human cells leads to the production of DSBs and activation of the DNA damage checkpoint. Finally, our evidence suggests that PLP deficiency threatens genome integrity, most likely via its role in dTMP biosynthesis, as Pdxk-deficient cells accumulate uracil in their nuclear DNA and are sensitive to inhibition of ribonucleotide reductase. Since Pdxk links diet to genome stability, our work supports the hypothesis that dietary micronutrients reduce cancer risk by curtailing the accumulation of DNA damage and suggests that micronutrient depletion could be part of a defense mechanism against hyperproliferation.
Author Summary
Cells must ensure the integrity of genetic information before cellular division. Loss of genome integrity is particularly germane to tumorigenesis, where it is thought to contribute to the rapid evolution of the malignant cell towards the fully cancerous phenotype. It is therefore imperative that we understand fully how cells maintain the integrity of the genome and how it is lost during tumorigenesis. In this study, we developed an assay that allowed us to systematically interrogate each gene of the budding yeast S. cerevisiae for its respective contribution to genome integrity. We report the identification of nine novel genes that increase the rate of genome instability in yeast when deleted. To our surprise, one of the genes we identified encodes the enzyme pyridoxal kinase, which acts in the metabolism of vitamin B6. We show that pyridoxal kinase influences genome stability by promoting the conversion of dietary vitamin B6 into its biologically active form, pyridoxal 5′ phosphate. Our work indicates that vitamin B6 metabolites are critical to maintain genome stability and supports a long-standing model, which hypothesizes that vitamin B6 reduces cancer risk by curtailing genome rearrangements.
PMCID: PMC1941753  PMID: 17696614
5.  Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study 
Genes & Nutrition  2014;9(3):403.
Micronutrient research typically focuses on analyzing the effects of single or a few nutrients on health by analyzing a limited number of biomarkers. The observational study described here analyzed micronutrients, plasma proteins, dietary intakes, and genotype using a systems approach. Participants attended a community-based summer day program for 6–14 year old in 2 years. Genetic makeup, blood metabolite and protein levels, and dietary differences were measured in each individual. Twenty-four-hour dietary intakes, eight micronutrients (vitamins A, D, E, thiamin, folic acid, riboflavin, pyridoxal, and pyridoxine) and 3 one-carbon metabolites [homocysteine (Hcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)], and 1,129 plasma proteins were analyzed as a function of diet at metabolite level, plasma protein level, age, and sex. Cluster analysis identified two groups differing in SAM/SAH and differing in dietary intake patterns indicating that SAM/SAH was a potential marker of nutritional status. The approach used to analyze genetic association with the SAM/SAH metabolites is called middle-out: SNPs in 275 genes involved in the one-carbon pathway (folate, pyridoxal/pyridoxine, thiamin) or were correlated with SAM/SAH (vitamin A, E, Hcy) were analyzed instead of the entire 1M SNP data set. This procedure identified 46 SNPs in 25 genes associated with SAM/SAH demonstrating a genetic contribution to the methylation potential. Individual plasma metabolites correlated with 99 plasma proteins. Fourteen proteins correlated with body mass index, 49 with group age, and 30 with sex. The analytical strategy described here identified subgroups for targeted nutritional interventions.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-014-0403-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4026438  PMID: 24760553
Systems nutrition; Methylation potential; SAM/SAH; Micronutrients; Community-based participatory research
6.  Eurocan plus report: feasibility study for coordination of national cancer research activities 
The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe–wide consultation ever conducted in the field of cancer research.
Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
It is essential to include the patients’ voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench–to–bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes, becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ organizations, European institutions, Member States, industry and small and medium enterprises (SMEs), putting into practice solutions aimed at alleviating barriers to collaboration and coordination of cancer research activities in the European Union, and dealing with legal and regulatory issues. The development of an effective ECI will require time, but this entity should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co–operation between comprehensive cancer centres and basic research laboratories throughout Europe and (3) networking between funding bodies at the European level.
The European Parliament and its instruments have had a major influence in cancer control in Europe, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
Executive Summary
Cancer is one of the biggest public health crises facing Europe in the 21st century—one for which Europe is currently not prepared nor preparing itself. Cancer is a major cause of death in Europe with two million casualties and three million new cases diagnosed annually, and the situation is set to worsen as the population ages.
These facts led the European Parliament, through the Research Directorate-General of the European Commission, to call for initiatives for better coordination of cancer research efforts in the European Union. The EUROCAN+PLUS Project was launched in October 2005 as a feasibility study for coordination of national cancer research activities. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people. In this respect, the Project became the largest Europe-wide consultation ever conducted in the field of cancer research, implicating researchers, cancer centres and hospitals, administrators, healthcare professionals, funding agencies, industry, patients’ organizations and patients.
The Project first identified barriers impeding research and collaboration in research in Europe. Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain the formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
In addition, there is a shortage of leadership, a multiplicity of institutions each focusing on its own agenda, sub–optimal contact with industry, inadequate training, non–existent career paths, low personnel mobility in research especially among clinicians and inefficient funding—all conspiring against efficient collaboration in cancer care and research. European cancer research today does not have a functional translational research continuum, that is the process that exploits biomedical research innovations and converts them into prevention methods, diagnostic tools and therapies. Moreover, epidemiological research is not integrated with other types of cancer research, and the implementation of the European Directives on Clinical Trials 1 and on Personal Data Protection 2 has further slowed the innovation process in Europe. Furthermore, large inequalities in health and research exist between the EU–15 and the New Member States.
The picture is not entirely bleak, however, as the European cancer research scene presents several strengths, such as excellent basic research and clinical research and innovative etiological research that should be better exploited.
When considering recommendations, several priority dimensions had to be retained. It is essential that proposals include actions and recommendations that can benefit all Member States of the European Union and not just States with the elite centres. It is also essential to have a broader patient orientation to help provide the knowledge to establish cancer control possibilities when we exhaust what can be achieved by the implementation of current knowledge. It is vital that the actions proposed can contribute to the Lisbon Strategy to make Europe more innovative and competitive in (cancer) research.
The Project participants identified six areas for which consensus solutions should be implemented in order to obtain better coordination of cancer research activities. The required solutions are as follows. The proactive management of innovation, detection, facilitation of collaborations and maintenance of healthy competition within the European cancer research community.The establishment of an exchange portal of information for health professionals, patients and policy makers.The provision of guidance for translational and clinical research including the establishment of a translational research platform involving comprehensive cancer centres and cancer research centres.The coordination of calls and financial management of cancer research projects.The construction of a ‘one–stop shop’ as a contact interface between the industry, small and medium enterprises, scientists and other stakeholders.The support of greater involvement of healthcare professionals in translational research and multidisciplinary training.
In the course of the EUROCAN+PLUS consultative process, several key collaborative projects emerged between the various groups and institutes engaged in the consultation. There was a collaboration network established with Europe’s leading Comprehensive Cancer Centres; funding was awarded for a closer collaboration of Owners of Cancer Registries in Europe (EUROCOURSE); there was funding received from FP7 for an extensive network of leading Biological Resource Centres in Europe (BBMRI); a Working Group identified the special needs of Central, Eastern and South–eastern Europe and proposed a remedy (‘Warsaw Declaration’), and the concept of developing a one–stop shop for dealing with academia and industry including the Innovative Medicines Initiative (IMI) was discussed in detail.
Several other dimensions currently lacking were identified. There is an absolute necessity to include the patients’ voice in the establishment of priority areas in cancer research at the present time. It was a salutary lesson when it was recognized that all that is known about the quality of life of the cancer patient comes from the experience of a tiny proportion of cancer patients included in a few clinical trials. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community was evident. A top priority should be the development of translational research (in its widest form) and the development of effective and innovative cancer treatments and preventative strategies in the European Union. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
Having taken note of the barriers and the solutions and having examined relevant examples of existing European organizations in the field, it was agreed during the General Assembly of 19 November 2007 that the EUROCAN+PLUS Project had to recommend the creation of a small, permanent and neutral ECI. This should be a model structure and was widely supported at both General Assemblies of the project. The proposal is based on the successful model of the European Molecular Biology Organisation (EMBO), and its principal aims include providing a forum where researchers from all backgrounds and from all countries can meet with members of other specialities including patients, nurses, clinicians, funders and scientific administrators to develop priority programmes to make Europe more competitive in research and more focused on the cancer patient.
The ECI should assume responsibility for: stimulating innovative cancer research and facilitating processes;becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ and organizations;European institutions, Member States, industry and small and medium enterprises;putting into practice the aforementioned solutions aimed at alleviating barriers and coordinating cancer research activities in the EU;dealing with legal and regulatory issues.
Solutions implemented through the ECI will lead to better coordination and collaboration throughout Europe, more efficient use of resources, an increase in Europe’s attractiveness to the biomedical industry and better quality of cancer research and education of health professionals.
The Project considered that European legal instruments currently available were inadequate for addressing many aspects of the barriers identified and for the implementation of effective, lasting solutions. Therefore, the legal environment that could shelter an idea like the ECI remains to be defined but should be done so as a priority. In this context, the initiative of the European Commission for a new legal entity for research infrastructure might be a step in this direction. The development of an effective ECI will require time, but this should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass: (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co-operation between comprehensive cancer centres and basic research laboratories throughout Europe; (3) networking between funding bodies at the European level. Another topic deserving immediate attention is the creation of a European database on cancer research projects and cancer research facilities.
Despite enormous progress in cancer control in Europe during the past two decades, there was an increase of 300,000 in the number of new cases of cancer diagnosed between 2004 and 2006. The European Parliament and its instruments have had a major influence in cancer control, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
PMCID: PMC3234055  PMID: 22274749
7.  A framework to explore micronutrient deficiency in maternal and child health in Malawi, Southern Africa 
Environmental Health  2009;8(Suppl 1):S13.
Global food insecurity is associated with micronutrient deficiencies and it has been suggested that 4.5 billion people world-wide are affected by deficiencies in iron, vitamin A and iodine. Zinc has also been identified to be of increasing concern. The most vulnerable are young children and women of childbearing age. A pilot study has been carried out in Southern Malawi, to attempt to link the geochemical and agricultural basis of micronutrient supply through spatial variability to maternal health and associated cultural and social aspects of nutrition. The aim is to establish the opportunity for concerted action to deliver step change improvements in the nutrition of developing countries.
Field work undertaken in August 2007 and July/August 2008 involved the collection of blood, soil and crop samples, and questionnaires from ~100 pregnant women. Complex permissions and authorisation protocols were identified and found to be as much part of the cultural and social context of the work as the complexity of the interdisciplinary project. These issues are catalogued and discussed. A preliminary spatial evaluation is presented linking soil quality and food production to nutritional health. It also considers behavioural and cultural attitudes of women and children in two regions of southern Malawi, (the Shire Valley and Shire Highlands plateau). Differences in agricultural practice and widely varying soil quality (e.g. pH organic matter, C/N and metal content) were observed for both regions and full chemical analysis of soil and food is underway. Early assessment of blood data suggests major differences in health and nutritional status between the two regions. Differences in food availability and type and observations of life style are being evaluated through questionnaire analysis.
The particular emphasis of the study is on the interdisciplinary opportunities and the barriers to progress in development support in subsistence communities. Engaging at the community level and the balance of expectations from both study subjects and research team highlight the merit of careful and detailed planning and project delivery.
PMCID: PMC2796491  PMID: 20102580
8.  Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review 
BMC Public Health  2012;12:506.
Micronutrient deficiency is a common public health problem in developing countries, especially for infants and children in the first two years of life. As this is an important time window for child development, micronutrient fortified complementary feeding after 6 months of age, for example with milk or cereals products, in combination with continued breastfeeding, is recommended. The overall effect of this approach is unclear.
We performed a Systematic Review and Meta-analysis to assess the impact of micronutrient fortified milk and cereal food on the health of infants and little children (aged 6 months to 5 years) compared to non-fortified food. We reviewed randomized controlled trials using electronic databases (MEDLINE and Cochrane library searches through FEB 2011), reference list screening and hand searches. Three reviewers assessed 1153 studies for eligibility and extracted data. One reviewer assessed risk of bias using predefined forms.
We included 18 trials in our analysis (n = 5’468 children; range of mean hemoglobin values: 9.0 to 12.6 g/dl). Iron plus multi micronutrient fortification is more effective than single iron fortification for hematologic outcomes. Compared to non-fortified food, iron multi micronutrient fortification increases hemoglobin levels by 0.87 g/dl (95%-CI: 0.57 to 1.16; 8 studies) and reduces risk of anemia by 57% (relative risk 0.43; 95%-CI 0.26 to 0.71; absolute risk reduction 22%; number needed to treat 5 [95%-CI: 4 to 6]; 6 Studies). Compared to non-fortified food, fortification increases serum levels of vitamin A but not of zinc. Information about functional health outcomes (e.g. weight gain) and morbidity was scarce and evidence is inconclusive. Risk of bias is unclear due to underreporting, but high quality studies lead to similar results in a sensitivity analysis.
Multi micronutrient fortified milk and cereal products can be an effective option to reduce anemia of children up to three years of age in developing countries. On the basis of our data the evidence for functional health outcomes is still inconclusive.
PMCID: PMC3444335  PMID: 22770558
Micronutrients; Fortification; Milk; Cereals
9.  A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn 
Trials  2011;12:60.
Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.
Methods and design
320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.
Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.
Trial registration
PMCID: PMC3059275  PMID: 21356082
10.  Tanzanian farmers' knowledge and attitudes to GM biotechnology and the potential use of GM crops to provide improved levels of food security. A Qualitative Study 
BMC Public Health  2010;10:407.
Genetically Modified (GM) crops have been championed as one possible method to improve food security and individual nutritional status in sub Saharan Africa. Understanding and acceptability of GM crop technology to farmers and consumers have not been assessed. We developed a qualitative research study involving farmers as both producers and consumers to gauge the understanding of GM crop technology, its acceptability, and identifying issues of concern.
Nineteen individual interviews (10 male and 9 female) and five mixed gender focus group discussions with local farmers were conducted in 3 regions in Tanzania. Analysis took place concurrently with data collection. Following initial interviews, subsequent questions were adjusted based on emerging themes.
Understanding, awareness and knowledge of GM crop technology and terminology and its potential risks and benefits was very poor in all regions. Receptivity to the potential use of GM crops was, however, high. Respondents focused on the potential benefits of GM crops rather than any potential longer term health risks. A number of factors, most significantly field trial data, would influence farmers' decisions regarding the introduction of GM crop varieties into their farming practice. Understanding of the potential improved health provision possible by changes in agricultural practice and food-related decision making, and the health benefits of a diet containing essential vitamins, minerals and micronutrients is also poor in these communities.
This study forms a basis from which further research work can be undertaken. It is important to continue to assess opinions and attitudes of farmers and consumers in sub Saharan Africa towards potential use of GM technologies whilst highlighting the importance of the relationship between agriculture, health and development. This will allow people in the region to make accurate, informed decisions about whether they believe use of GM biotechnology is an appropriate way in which to tackle issues of food security, provide improved health and drive development.
PMCID: PMC2912813  PMID: 20624286
11.  Nutrigenetics, Nutrigenomics, and Selenium 
Selenium (Se) is an important micronutrient that, as a component of selenoproteins, influences oxidative and inflammatory processes. Its’ levels vary considerably, with different ethnic and geographic population groups showing varied conditions, ranging from frank Se deficiencies to toxic effects. An optimum Se level is essential for the maintenance of homeostasis, and this optimum may vary according to life stage, general state of health, and genotype. Nutrigenetic studies of different Se levels, in the presence of genetic variants in selenoproteins, suggest that an effective dietary Se intake for one individual may be very different from that for others. However, we are just starting to learn the significance of various genes in selenoprotein pathways, functional variants in these, and how to combine such data from genes into pathways, alongside dietary intake or serum levels of Se. Advances in systems biology, genetics, and genomics technologies, including genetic/genomic, epigenetic/epigenomic, transcriptomic, proteomic, and metabolomic information, start to make it feasible to assess a comprehensive spectrum of the biological activity of Se. Such nutrigenomic approaches may prove very sensitive biomarkers of optimal Se status at the individual or population level. The premature cessation of a major human Se intervention trial has led to considerable controversy as to the value of Se supplementation at the population level. New websites provide convenient links to current information on methodologies available for nutrigenetics and nutrigenomics. These new technologies will increasingly become an essential tool in optimizing the level of Se and other micronutrients for optimal health, in individuals and in population groups. However, definitive proof of such effects will require very large collaborative studies, international agreement on study design, and innovative approaches to data analysis.
PMCID: PMC3268570  PMID: 22303312
selenium; selenoprotein; nutrigenetics; nutrigenomics
12.  Vitamin/Trace Mineral Supplements for the Elderly1 
Advances in Nutrition  2012;3(6):822-824.
The fraction of population that is elderly has been increasing, as has the consumption of vitamin/trace mineral supplements, which is now a multibillion dollar industry. Yet the rationale for such supplement intake by the majority may be questioned. Some of the current recommendations for micronutrient intake by the elderly are extrapolations from recommendations made for younger adults, whereas other recommendations are based on measurements of biochemical indices not proven to reflect a deficient level in the elderly. Suggestions that the elderly need more than the recommended daily allowances largely rest on the assumption that they should have biochemical indices similar to younger adults despite decreased energy intake with decreased physical and metabolic activities of the elderly. Although some individuals require supplementation because of problems with intake, absorption, or metabolism, there is little or no proof that boosting micronutrient intake above what can be achieved in well-balanced diets, some of which already contain fortified foods, will lead to a healthier outcome for most elderly individuals. There is not only the potential for unnecessary and occasionally harmful excess administered to some, but there is a cost that now runs in the billions of dollars and adds to the costs of covering multiple chronic disease conditions. Hence, some caution should be exercised in public health promulgations concerning routine use of supplements for those in this age group (>65 y of age) and of both sexes until more research establishes clear connections between the need for micronutrients and nutrient-related health in the elderly.
PMCID: PMC3648707  PMID: 23153737
13.  Genetic and environmental influences on nutrient intake 
Genes & Nutrition  2012;8(2):241-252.
The relationship between genetic and the environment represents a pathway to better understand individual variations in nutrition intake and food preferences. However, the present literature is weakened somewhat by methodological flaws (e.g., overreliance on self-report questionnaires), discrepancies in statistical approaches, and inconsistent findings. Little research on this topic to date has included examination of micronutrient intake. The purpose of this study is to improve the existing literature on genetic and environmental influences on energy and nutrient intake by addressing these gaps. Twin pairs (N = 358; age 11–13 years) provided 3-day food intake diaries, which were assessed for intake of total energy, macronutrients, and micronutrients. Structural equation modeling revealed that genetic influences accounted for a significant portion of the total variance in total energy (48 %), macronutrients (35–45 %), minerals (45 %), and vitamins (21 %). Consistent with previous studies, the shared environment appeared to contribute little to nutritional intake. Findings on vitamin and mineral intake are novel and are particularly beneficial for further research on the contribution of micronutrients to individual physical health status. Better understanding of the linkage between genes, environment, and nutritional intake and deficiencies can clarify behavioral and physical outcomes, potentially informing risk reduction, primary prevention, and intervention strategies.
PMCID: PMC3575882  PMID: 23055091
Twin; Genes; Nutrient; Diet; Heritability; Environment
14.  Prevalence of anemia and deficiency of iron, folic acid, and zinc in children younger than 2 years of age who use the health services provided by the Mexican Social Security Institute 
BMC Public Health  2007;7:345.
In Mexico, as in other developing countries, micronutrient deficiencies are common in infants between 6 and 24 months of age and are an important public health problem. The objective of this study was to determine the prevalence of anemia and of iron, folic acid, and zinc deficiencies in Mexican children under 2 years of age who use the health care services provided by the Mexican Institute for Social Security (IMSS).
A nationwide survey was conducted with a representative sample of children younger than 2 years of age, beneficiaries, and users of health care services provided by IMSS through its regular regimen (located in urban populations) and its Oportunidades program (services offered in rural areas). A subsample of 4,955 clinically healthy children was studied to determine their micronutrient status. A venous blood sample was drawn to determine hemoglobin, serum ferritin, percent of transferrin saturation, zinc, and folic acid. Descriptive statistics include point estimates and 95% confidence intervals for the sample and projections for the larger population from which the sample was drawn.
Twenty percent of children younger than 2 years of age had anemia, and 27.8% (rural) to 32.6% (urban) had iron deficiency; more than 50% of anemia was not associated with low ferritin concentrations. Iron stores were more depleted as age increased. Low serum zinc and folic acid deficiencies were 28% and 10%, respectively, in the urban areas, and 13% and 8%, respectively, in rural areas. The prevalence of simultaneous iron and zinc deficiencies was 9.2% and 2.7% in urban and rural areas. Children with anemia have higher percentages of folic acid deficiency than children with normal iron status.
Iron and zinc deficiencies constitute the principal micronutrient deficiencies in Mexican children younger than 2 years old who use the health care services provided by IMSS. Anemia not associated with low ferritin values was more prevalent than iron-deficiency anemia. The presence of micronutrient deficiencies at this early age calls for effective preventive public nutrition programs to address them.
PMCID: PMC2244632  PMID: 18053140
15.  Micronutrient intake in relation to all-cause mortality in a prospective Danish cohort 
Food & Nutrition Research  2012;56:10.3402/fnr.v56i0.5466.
Few studies have considered source-specific micronutrient intake in relation to mortality under the consideration that dietary and supplemental intake could exhibit different effects.
To evaluate the association between intake of vitamin C, E, folate, beta-carotene from diet and supplements, and overall mortality. Furthermore, to examine effect modification by smoking, alcohol intake, and BMI and to investigate if the effect of supplement use differs with dietary micronutrient intake.
Methods and Material
In a prospective cohort study of 55,453 middle-aged Danes, information regarding diet, supplement use, and lifestyle was collected through questionnaires. During follow-up, 6,767 deaths were identified and incidence rate ratios (IRRs) of mortality related to micronutrient intake were calculated using Cox proportional hazards models.
The present study found no effect of dietary vitamin C, E, folate, or beta-carotene in relation to mortality. In contrast, supplemental folic acid was associated with a significantly increased mortality, whereas no other micronutrient supplement was associated with mortality. Effect modification by smoking and alcohol intake, but not BMI, was suggested in relation to some dietary micronutrients. The effect of supplements did not differ in groups defined by dietary micronutrient intake.
This study suggests no effect of dietary micronutrients in relation to overall mortality. Supplemental folic acid was found to be associated with increased mortality, but further studies are required. No other supplemental micronutrient was associated with mortality.
PMCID: PMC3321248  PMID: 22489215
mortality; dietary supplements; micronutrients; prospective cohort study; vitamin C; vitamin E; folate; beta-carotene
16.  Transformations of summary statistics as input in meta-analysis for linear dose-response models on a logarithmic scale: a methodology developed within EURRECA 
To derive micronutrient recommendations in a scientifically sound way, it is important to obtain and analyse all published information on the association between micronutrient intake and biochemical proxies for micronutrient status using a systematic approach. Therefore, it is important to incorporate information from randomized controlled trials as well as observational studies as both of these provide information on the association. However, original research papers present their data in various ways.
This paper presents a methodology to obtain an estimate of the dose–response curve, assuming a bivariate normal linear model on the logarithmic scale, incorporating a range of transformations of the original reported data.
The simulation study, conducted to validate the methodology, shows that there is no bias in the transformations. Furthermore, it is shown that when the original studies report the mean and standard deviation or the geometric mean and confidence interval the results are less variable compared to when the median with IQR or range is reported in the original study.
The presented methodology with transformations for various reported data provides a valid way to estimate the dose–response curve for micronutrient intake and status using both randomized controlled trials and observational studies.
PMCID: PMC3780718  PMID: 22533574
Methodology; Dose–response; Meta-analysis; EURRECA
17.  Commercial weight loss diets meet nutrient requirements in free living adults over 8 weeks: A randomised controlled weight loss trial 
Nutrition Journal  2008;7:25.
To investigate the effect of commercial weight loss programmes on macronutrient composition and micronutrient adequacy over a 2 month period.
Adults were randomly allocated to follow the Slim Fast Plan, Weight Watchers Pure Points Programme, Dr Atkins' New Diet Revolution, or Rosemary Conley's "Eat Yourself Slim" Diet & Fitness Plan.
A multi-centre randomised controlled trial.
293 adults, mean age 40.3 years and a mean BMI 31.7 (range 27–38) were allocated to follow one of the four diets or control group. Subjects completed a 7-day food and activity diary at baseline (prior to randomisation) and after 2 months. Diet records were analysed for nutrient composition using WinDiets (research version).
A significant shift in the macronutrient composition of the diet with concurrent alteration of the micronutrient profile was apparent with all diets. There was no evidence to suggest micronutrient deficiency in subjects on any of the dietary regimens. However, those sub-groups with higher needs for specific micronutrients, such as folate, iron or calcium may benefit from tailored dietary advice.
The diets tested all resulted in considerable macronutrient change and resulted in an energy deficit indicating dietary compliance. Health professionals and those working in community and public health should be reassured of the nutritional adequacy of the diets tested.
Trial Registration Number
PMCID: PMC2551603  PMID: 18764946
18.  Evidence to support a food-based dietary guideline on sugar consumption in South Africa 
BMC Public Health  2012;12:502.
To review studies undertaken in South Africa (SA) which included sugar intake associated with dental caries, non-communicable diseases, diabetes, obesity and/or micronutrient dilution, since the food-based dietary guideline: “Use foods and drinks that contain sugar sparingly and not between meals” was promulgated by the Department of Health (DOH) in 2002.
Three databases (PubMed, Cochrane Library, and ScienceDirect), and SA Journal of Clinical Nutrition (SAJCN), DOH and SA Medical Research Council (SAMRC) websites were searched for SA studies on sugar intake published between 2000 and January 2012. Studies were included in the review if they evaluated the following: sugar intake and dental caries; sugar intake and non-communicable diseases; sugar and diabetes; sugar and obesity and/or sugar and micronutrient dilution.
The initial search led to 12 articles in PubMed, 0 in Cochrane, 35 in ScienceDirect, 5 in the SAJCN and 3 reports from DOH/SAMRC. However, after reading the abstracts only 7 articles from PubMed, 4 from SAJCN and 3 reports were retained for use as being relevant to the current review. Hand searching of reference lists of SAJCN articles produced two more articles. Intake of sugar appears to be increasing steadily across the South African (SA) population. Children typically consume about 50 g per day, rising to as much as 100 g per day in adolescents. This represents about 10% of dietary energy, possibly as much as 20%. It has been firmly established that sugar plays a major role in development of dental caries. Furthermore, a few studies have shown that sugar has a diluting effect on the micronutrient content of the diet which lowers the intake of micronutrients. Data from numerous systematic reviews have shown that dietary sugar increases the risk for development of both obesity and type 2 diabetes. Risk for development of these conditions appears to be especially strong when sugar is consumed as sugar-sweetened beverages.
Based on the evidence provided the current DOH food-based dietary guideline on sugar intake should remain as is.
PMCID: PMC3439261  PMID: 22762394
19.  Prevalence of micronutrient deficiency in popular diet plans 
Research has shown micronutrient deficiency to be scientifically linked to a higher risk of overweight/obesity and other dangerous and debilitating diseases. With more than two-thirds of the U.S. population overweight or obese, and research showing that one-third are on a diet at any given time, a need existed to determine whether current popular diet plans could protect followers from micronutrient deficiency by providing the minimum levels of 27 micronutrients, as determined by the U.S. Food and Drug Administrations (FDA) Reference Daily Intake (RDI) guidelines.
Suggested daily menus from four popular diet plans (Atkins for Life diet, The South Beach Diet, the DASH diet, the DASH diet) were evaluated. Calorie and micronutrient content of each ingredient, in each meal, were determined by using food composition data from the U.S. Department of Agriculture Nutrient Database for Standard Reference. The results were evaluated for sufficiency and total calories and deficient micronutrients were identified. The diet plans that did not meet 100% sufficiency by RDI guidelines for each of the 27 micronutrients were re-analyzed; (1) to identify a micronutrient sufficient calorie intake for all 27 micronutrients, and (2) to identify a second micronutrient sufficient calorie intake when consistently low or nonexistent micronutrients were removed from the sufficiency requirement.
Analysis determined that each of the four popular diet plans failed to provide minimum RDI sufficiency for all 27 micronutrients analyzed. The four diet plans, on average, were found to be RDI sufficient in (11.75 ± 2.02; mean ± SEM) of the analyzed 27 micronutrients and contain (1748.25 ± 209.57) kcal. Further analysis of the four diets found that an average calorie intake of (27,575 ± 4660.72) would be required to achieve sufficiency in all 27 micronutrients. Six micronutrients (vitamin B7, vitamin D, vitamin E, chromium, iodine and molybdenum) were identified as consistently low or nonexistent in all four diet plans. These six micronutrients were removed from the sufficiency requirement and additional analysis of the four diets was conducted. It was determined that an average calorie content of (3,475 ± 543.81) would be required to reach 100% sufficiency in the remaining 21 micronutrients.
These findings are significant and indicate that an individual following a popular diet plan as suggested, with food alone, has a high likelihood of becoming micronutrient deficient; a state shown to be scientifically linked to an increased risk for many dangerous and debilitating health conditions and diseases.
PMCID: PMC2905334  PMID: 20537171
20.  Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project 
PLoS Genetics  2008;4(6):e1000095.
Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the microbial marine community derived from the Global Ocean Sampling (GOS) expedition. More than 3,600 selenoprotein gene sequences belonging to 58 protein families were detected, including sequences representing 7 newly identified selenoprotein families, such as homologs of ferredoxin–thioredoxin reductase and serine protease. In addition, a new eukaryotic selenoprotein family, thiol reductase GILT, was identified. Most GOS selenoprotein families originated from Cys-containing thiol oxidoreductases. In both Pacific and Atlantic microbial communities, SelW-like and SelD were the most widespread selenoproteins. Geographic location had little influence on Sec utilization as measured by selenoprotein variety and the number of selenoprotein genes detected; however, both higher temperature and marine (as opposed to freshwater and other aquatic) environment were associated with increased use of this amino acid. Selenoproteins were also detected with preference for either environment. We identified novel fusion forms of several selenoproteins that highlight redox activities of these proteins. Almost half of Cys-containing SelDs were fused with NADH dehydrogenase, whereas such SelD forms were rare in terrestrial organisms. The selenouridine utilization trait was also analyzed and showed an independent evolutionary relationship with Sec utilization. Overall, our study provides insights into global trends in microbial selenium utilization in marine environments.
Author Summary
Selenium (Se) is an essential micronutrient due to its requirement for biosynthesis and function of the 21st amino acid, selenocysteine (Sec). Sec is found in the active sites of selenoproteins, most of which exhibit redox function, in all three domains of life. In recent years, genome sequencing projects provided a large volume of nucleotide and protein sequence information. Identification of complete sets of selenoproteins (selenoproteomes) of individual organisms and environmental samples is important for better understanding of Se utilization, biological functions of this element, and changes in Se use during evolution. Here, we describe a comprehensive analysis of the selenoproteome of the microbial marine community derived from the Global Ocean Sampling (GOS) expedition. More than 3,600 selenoprotein gene sequences belonging to 58 protein families were detected and analyzed. Our study generated the largest selenoproteome reported to date and provided important insights into microbial Se utilization and its evolutionary trends in marine environments.
PMCID: PMC2398784  PMID: 18551170
21.  How to reach a common estimate of high dietary micronutrient intakes for safe addition of vitamins and minerals to foods? 
Food & Nutrition Research  2009;53:10.3402/fnr.v53i0.1898.
A central element in establishing maximum amount of micronutrients in fortified foods and supplements is to reach to an agreement on how to estimate high intakes of vitamins and minerals from the European diet.
To examine whether ratios between the 95th percentile and mean intakes of vitamins and minerals show similarities across different countries independent of dietary habits and survey methods and if so, to suggest a simple and pragmatic way to calculate common estimates of high micronutrient intakes from foods.
Intake data of selected vitamins and minerals from nine European countries were examined for adult females and males and for children aged 4–10 and 11–17 years. The ratios between the 95th percentile and mean intakes were calculated for each micronutrient, country, and age group.
The ratios for each micronutrient follow a fairly regular pattern across countries and survey methods with differences between age groups.
The nutrients fall into three categories: nutrients with ratios between 1.45 and 1.58 – energy, magnesium, phosphorus, zinc, iron, vitamin B6, niacin, and folate; nutrients with ratios between 1.67 and 1.79 – calcium, selenium, vitamin E, iodine, and copper; nutrients with ratios between 2.08 and 2.32 – vitamin A, vitamin D, and retinol.
Sufficiently precise estimates of high micronutrient intakes across European countries can be reached by multiplying the overall average of ratios (P95/mean intakes) for each micronutrient with the corresponding mean intakes from all available dietary surveys in Europe. This approach is a simple and pragmatic way to create common European estimates of high micronutrient intakes from foods.
PMCID: PMC2767238  PMID: 19859554
95th percentile; mean; ratio; dietary surveys
22.  Gastric and intestinal barrier impairment in tropical enteropathy and HIV: limited impact of micronutrient supplementation during a randomised controlled trial 
BMC Gastroenterology  2010;10:72.
Although micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood. We tested the hypothesis that micronutrient supplementation can enhance barrier function of the gut.
We carried out two sub-studies nested within a randomised, double-blind placebo-controlled trial of daily micronutrient supplementation in an urban community in Lusaka, Zambia. In the first sub-study, gastric pH was measured in 203 participants. In the second sub-study, mucosal permeability, lipopolysaccharide (LPS) and anti-LPS antibodies, and serum soluble tumour necrosis factor receptor p55 (sTNFR55) concentrations were measured in 87 participants. Up to three stool samples were also analysed microbiologically for detection of asymptomatic intestinal infection. Gastric histology was subsequently analysed in a third subset (n = 37) to assist in interpretation of the pH data. Informed consent was obtained from all participants after a three-stage information and consent process.
Hypochlorhydria (fasting gastric pH > 4.0) was present in 75 (37%) of participants. In multivariate analysis, HIV infection (OR 4.1; 95%CI 2.2-7.8; P < 0.001) was associated with hypochlorhydria, but taking anti-retroviral treatment (OR 0.16; 0.04-0.67; P = 0.01) and allocation to micronutrient supplementation (OR 0.53; 0.28-0.99; P < 0.05) were protective. Hypochlorhydria was associated with increased risk of salmonellosis. Mild (grade 1) gastric atrophy was found in 5 participants, irrespective of Helicobacter pylori or HIV status. Intestinal permeability, LPS concentrations in serum, anti-LPS IgG, and sTNFR55 concentrations did not differ significantly between micronutrient and placebo groups. Anti-LPS IgM was reduced in the micronutrient recipients (P <0.05).
We found evidence of a specific effect of HIV on gastric pH which was readily reversed by anti-retroviral therapy and not mediated by gastric atrophy. Micronutrients had a modest impact on gastric pH and one marker of bacterial translocation.
Trial Registration
Current Controlled Trials ISRCTN31173864
PMCID: PMC2910659  PMID: 20604937
23.  The Extended Nutrigenomics – Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host 
Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host’s life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host’s genome, and calls for an “extended nutrigenomics” approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes, proteomes, transcriptomes, and metabolomes under the definition of genomics as the overarching term covering essentially all Omics rather than the sole study of DNA and RNA.
PMCID: PMC3268576  PMID: 22303317
nutrigenomics; nutrigenetics; epigenetics; personalized nutrition; biomarker; bioactive; gut microbiota
24.  Biofortification in China: policy and practice 
Micronutrient deficiency undernutrition, due to insufficient levels of vitamins and minerals in the diet, remains one of the most prevalent and preventable nutritional problems in the world today. Micronutrient undernutrition is the most common form of malnutrition. Compared to the 180 million children with protein-energy malnutrition, 3.5–5 billion persons are iron-deficient, and 140–250 million persons are vitamin A-deficient. Micronutrient deficiencies diminish physical, cognitive, and reproductive development. Undernutrition is both a cause and a result of poor human health and achievement.
Middle-income nations, such as China, also suffer from micronutrient undernutrition's effects. In China's poor western provinces, despite supplementation and fortification efforts, stunting and underweight (symptoms of micronutrient undernutrition) remain common. In recent decades, nutritional adequacy, in terms of available food energy, improved immensely, as the government made food security a top priority. A potential next step for China could be to address specifically micronutrient undernutrition. The paper aims to provide a discussion of policy issues relevant to biofortification, if China were to consider the implementation of this intervention in its rural provinces.
Traditional nutritional interventions currently employ four main strategies: dietary modification, supplementation, commercial fortification, and biofortification. Biofortification, a relatively new technique, involves selectively breeding staple plant varieties to increase specific nutrient levels in plant tissues. Biofortification has the potential to provide benefits to humans, plants, and livestock; nourish nutrient-depleted soils; and help increase crop yields per acre. Biofortification methods include selective breeding, reducing levels of anti-nutrients, and increasing levels of substances that promote nutrient absorption.
If China were to implement biofortification programs, with help from government agencies and international organizations, several policy questions would need to be addressed. The paper discusses several policy questions that pertain to the relationship between biofortified and genetically modified crops, human health and safety concerns, labeling of biofortified crops for consumers, consumer rights, potential environmental impacts, intellectual property rights, seed disbursement, government investment, private-sector research, and additional agricultural and commercial regulations. Biofortification has the potential to help alleviate the suffering, death, disability, and failure to achieve full human potential that results from micronutrient undernutrition-related diseases.
PMCID: PMC2092419  PMID: 17897456
25.  Complementary feeding: a Global Network cluster randomized controlled trial 
BMC Pediatrics  2011;11:4.
Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated.
A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial.
Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children.
Trial registration
PMCID: PMC3032692  PMID: 21232139

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