Michael Hambidge

Human zinc deficiency

The objective of this paper is to provide a current overview of the significance of zinc in human nutrition. To achieve this, the following issues are addressed: (1) the biochemistry and biology of zinc in the context of their relevance to zinc in human nutrition and to our understanding of the complexity and practical importance of human zinc deficiency; (2) the history of our understanding of human zinc deficiency with an emphasis both on its brevity and on notable recent progress; (3) the clinical spectrum of severe zinc deficiency; (4) the lack of ideal biomarkers for milder zinc deficiency states, with the consequent dependence on randomized, placebo-controlled intervention studies to ascertain their prevalence and clinical consequences, including growth delay, diarrhea, pneumonia, other infections, disturbed neuropsychological performance and abnormalities of fetal development; (5) the public health significance of human zinc deficiency in the developing world; (6) reasons for concern and unanswered questions about zinc nutriture in the United States; (7) the need for better understanding of human zinc metabolism and homeostasis (including its limitations) at a molecular, cellular, organ-system and whole body level and of factors that affect zinc bioavailability; and (8) potential strategies for the prevention and management of human zinc deficiency. This review concludes with an emphasis on the immediate need for expanded research in directions that have become increasingly well demarcated and impelling as a result of recent progress, which is summarized in this overview.

Clinical conditions altering copper metabolism in humans.

Overt copper deficiency is not believed to be a widespread public health concern for most population groups. However, a variety of case studies suggest that under certain circumstances, clinical conditions may predispose individuals to the risk of copper deficiency or copper excess. Acquired copper deficiency has been documented in conditions predisposing to inadequate copper intakes, in prematurity, in malabsorption syndromes, and in conditions predisposing to excessive copper losses. In contrast, increases in copper concentrations have been reported in response to stress, inflammation, and infection; in Parkinson disease and diabetes mellitus; and in conditions involving an obstruction to bile flow.

The usefulness of in vitro models to predict the bioavailability of iron and zinc: A consensus statement from the HarvestPlus expert consultation

A combination of dietary and host-related factors determines iron and zinc absorption, and several in vitro methods have been developed as preliminary screening tools for assessing bioavailability. An expert committee has reviewed evidence for their usefulness and reached a consensus. Dialyzability (with and without simulated digestion) gives some useful information but cannot predict the correct magnitude of response and may sometimes predict the wrong direction of response. Caco-2 cell systems (with and without simulated digestion) have been developed for iron availability, but the magnitude of different effects does not always agree with results obtained in human volunteers, and the data for zinc are too limited to draw conclusions about the validity of the method. Caco-2 methodologies vary significantly between laboratories and require experienced technicians and good quality cell culture facilities to obtain reproducible results. Algorithms can provide semi-quantitative information enabling diets to be classified as high, moderate, or low bioavailability. While in vitro methods can be used to generate ideas and develop hypotheses, they cannot be used alone for important decisions concerning food fortification policy, selection of varieties for plant breeding programs, or for new product development in the food industry. Ultimately human studies are required for such determinations.

Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions

This paper resulted from a conference entitled “Lactation and Milk: Defining and refining the critical questions” held at the University of Colorado School of Medicine from January 18–20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond.

Outcomes from a School-based Nutrition Education Program Using Resource Teachers and Cross-disciplinary Models

Abstract The Integrated Nutrition Project is an ongoing comprehensive elementary school-based program focused on increasing consumption of whole grains, fruits, and vegetables in children and establishing nutrition education in the schools through local partnerships. This paper reports on years three and four outcomes. It was hypothesized that blending Social Cognitive Theory with the educational philosophies of Piaget and Dewey would enhance behavior change. The primary intervention consisted of (1) 24 weekly hands-on activities taught by a resource teacher and (2) six parent-taught lunchroom “mini-lessons.” Classroom activities were designed to reinforce concepts in math, science, literacy, and social studies. The quasi-experimental design used classrooms in matched schools; 20 and 17 classes were in treatment and comparison conditions, respectively, in year four. Surveys, interviews, and lunchroom plate waste were used to assess children; teachers were interviewed. Students in treatment classrooms achieved significantly greater gains in knowledge and self-efficacy regarding food preparation and fruit and vegetable consumption and consumed 0.4 more National Cancer Institute equivalent servings of fruits and vegetables in the lunchroom. Teachers responded favorably to the resource teacher model and the hands-on approach. The projects outcomes were attributed to the interventions theory-based behavior change focus and the use of a resource teacher who ensured consistent delivery of the intervention. Program implications include the need to explore variations of the resource teacher model and the potential for implementation on a larger scale.

High Mortality Rates for Very Low Birth Weight Infants in Developing Countries Despite Training

OBJECTIVE: The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants. METHODS: Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP. RESULTS: A total of 1096 VLBW (500–1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training. CONCLUSIONS: Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected.

Assessment of zinc status in man

ConclusionsThe assessment of human zinc nutritional status has proven to be difficult and challenging task over the course of many years. Dietary and medical history and physical examination may all provide important clues. Of the many laboratory assays for measurement of tissue zinc concentration and functional indices of zinc status, plasma zinc, despite many limitations, remains the assay of choice. Utilization of stable isotope techniques to evaluate zinc homeostasis include measurement of absorption of exogenous zinc, excretion of endogenous zinc and estimation of the combined size of the pools of zinc that are readily available on a whole organism level. Such measurements are starting to yield useful new insights into zinc status. While this approach appears to offer the potential for significant progress on a research basis, it does not provide techniques that are readily applied on a large scale or under ‘field’ conditions. Carefully designed, randomized, placebo controlled supplementation trials are almost invariably required to delineate the clinical and metabolic effects of correcting putative deficiency states. In the case of zinc, these can serve the additional role of confirming the underlying zinc deficiency state.

Underwood Memorial Lecture Human Zinc Homeostasis: Good but Not Perfect

Three selected aspects of human zinc homeostasis and requirements are reviewed with special reference to studies undertaken by the author and his colleagues: 1) the implications for the calculation of physiologic requirements for zinc of the interrelationship between two key variables of zinc homeostasis, intestinal excretion of endogenous zinc and total absorbed zinc, are examined at levels of absorption below those necessary to meet physiologic requirements; 2) a method for deriving average dietary zinc requirements from zinc-stable isotope tracer/metabolic studies is illustrated with examples of studies being conducted in developing countries; and 3) the effect of reduction of high intakes of phytic acid on zinc bioavailability is examined with test meals prepared from low-phytic-acid maize or isohybrid wild-type control maize.

Hemoglobin, Growth, and Attention of Infants in Southern Ethiopia

Male and female infants from rural Ethiopia were tested to investigate relations among hemoglobin (Hb), anthropometry, and attention. A longitudinal design was used to examine differences in attention performance from 6 (M = 24.9 weeks, n = 89) to 9 months of age (M = 40.6 weeks, n = 85), differences hypothesized to be related to changes in iron status and growth delays. Stunting (length-for-age z scores < -2.0) and attention performance, t(30) = -2.42, p = .022, worsened over time. Growth and Hb predicted attention at 9 months, R(2) = .15, p < .05, but not at 6. The study contributes to the knowledge base concerning the relations among Hb, early growth, and attention.

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings

BackgroundTo describe quantitative data quality monitoring and performance metrics adopted by the Global Network’s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs).MethodsOngoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013.ResultsDelivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time.ConclusionHigh quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.Trial registration numberNCT01073475