Michael B. Zimmermann

Nutritional iron deficiency

Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming monotonous plant-based diets. The high prevalence of iron deficiency in the developing world has substantial health and economic costs, including poor pregnancy outcome, impaired school performance, and decreased productivity. Recent studies have reported how the body regulates iron absorption and metabolism in response to changing iron status by upregulation or downregulation of key intestinal and hepatic proteins. Targeted iron supplementation, iron fortification of foods, or both, can control iron deficiency in populations. Although technical challenges limit the amount of bioavailable iron compounds that can be used in food fortification, studies show that iron fortification can be an effective strategy against nutritional iron deficiency. Specific laboratory measures of iron status should be used to assess the need for fortification and to monitor these interventions. Selective plant breeding and genetic engineering are promising new approaches to improve dietary iron nutritional quality.

Iodine-deficiency disorders.

2 billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficiency disorders. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Assessment methods include urinary iodine concentration, goitre, newborn thyroid-stimulating hormone, and blood thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is iodisation of salt, which is one of the most cost-effective ways to contribute to economic and social development. When iodisation of salt is not possible, iodine supplements can be given to susceptible groups. Introduction of iodised salt to regions of chronic iodine-deficiency disorders might transiently increase the proportion of thyroid disorders, but overall the small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. International efforts to control iodine-deficiency disorders are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges.

Evidence that the prevalence of childhood overweight is plateauing: data from nine countries

Until quite recently, there has been a widespread belief in the popular media and scientific literature that the prevalence of childhood obesity is rapidly increasing. However, high quality evidence has emerged from several countries suggesting that the rise in the prevalence has slowed appreciably, or even plateaued. This review brings together such data from nine countries (Australia, China, England, France, Netherlands, New Zealand, Sweden, Switzerland and USA), with data from 467,294 children aged 2-19 years. The mean unweighted rate of change in prevalence of overweight and obesity was +0.00 (0.49)% per year across all age ×sex groups and all countries between 1995 and 2008. For overweight alone, the figure was +0.01 (0.56)%, and for obesity alone -0.01 (0.24)%. Rates of change differed by sex, age, socioeconomic status and ethnicity. While the prevalence of overweight and obesity appears to be stabilizing at different levels in different countries, it remains high, and a significant public health issue. Possible reasons for the apparent flattening are hypothesised.

Global Iodine Status in 2011 and Trends over the Past Decade

Salt iodization has been introduced in many countries to control iodine deficiency. Our aim was to assess global and regional iodine status as of 2011 and compare it to previous WHO estimates from 2003 and 2007. Using the network of national focal points of the International Council for the Control of Iodine Deficiency Disorders as well as a literature search, we compiled new national data on urinary iodine concentration (UIC) to add to the existing data in the WHO Vitamin and Mineral Nutrition Information System Micronutrients Database. The most recent data on UIC, primarily national data in school-age children (SAC), were analyzed. The median UIC was used to classify national iodine status and the UIC distribution to estimate the number of individuals with low iodine intakes by severity categories. Survey data on UIC cover 96.1% of the worlds population of SAC, and since 2007, new national data are available for 58 countries, including Canada, Pakistan, the U.K., and the U.S.. At the national level, there has been major progress: from 2003 to 2011, the number of iodine-deficient countries decreased from 54 to 32 and the number of countries with adequate iodine intake increased from 67 to 105. However, globally, 29.8% (95% CI = 29.4, 30.1) of SAC (241 million) are estimated to have insufficient iodine intakes. Sharp regional differences persist; southeast Asia has the largest number of SAC with low iodine intakes (76 million) and there has been little progress in Africa, where 39% (58 million) have inadequate iodine intakes. In summary, although iodine nutrition has been improving since 2003, global progress may be slowing. Intervention programs need to be extended to reach the nearly one-third of the global population that still has inadequate iodine intakes.

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d'Ivoire

BACKGROUND Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274.

Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review

The World Health Organization (WHO) recently increased their recommended iodine intake during pregnancy from 200 to 250 microg/d and suggested that a median urinary iodine (UI) concentration of 150-249 microg/L indicates adequate iodine intake in pregnant women. Thyrotropin concentrations in blood collected from newborns 3-4 d after birth may be a sensitive indicator of even mild iodine deficiency during late pregnancy; a <3% frequency of thyrotropin values >5 mU/L indicates iodine sufficiency. New reference data and a simple collection system may facilitate use of the median UI concentration as an indicator of iodine status in newborns. In areas of severe iodine deficiency, maternal and fetal hypothyroxinemia can cause cretinism and adversely affect cognitive development in children; to prevent fetal damage, iodine should be given before or early in pregnancy. Whether mild-to-moderate maternal iodine deficiency produces more subtle changes in cognitive function in offspring is unclear; no controlled intervention studies have measured long-term clinical outcomes. Cross-sectional studies have, with few exceptions, reported impaired intellectual function and motor skills in children from iodine-deficient areas, but many of these studies were likely confounded by other factors that affect child development. In countries or regions where <90% of households are using iodized salt and the median UI concentration in school-age children is <100 microg/L, the WHO recommends iodine supplementation in pregnancy and infancy.

Assessment of iodine nutrition in populations: past, present, and future

Iodine status has been historically assessed by palpation of the thyroid and reported as goiter rates. Goiter is a functional biomarker that can be applied to both individuals and populations, but it is subjective. Iodine status is now assessed using an objective biomarker of exposure, i.e., urinary iodine concentrations (UICs) in spot samples and comparison of the median UIC to UIC cut-offs to categorize population status. This has improved standardization, but inappropriate use of the crude proportion of UICs below the cut-off level of 100 µg/L to estimate the number of iodine-deficient children has led to an overestimation of the prevalence of iodine deficiency. In this review, a new approach is proposed in which UIC data are extrapolated to iodine intakes, adjusted for intraindividual variation, and then interpreted using the estimated average requirement cut-point model. This may allow national programs to define the prevalence of iodine deficiency in the population and to quantify the necessary increase in iodine intakes to ensure sufficiency. In addition, thyroglobulin can be measured on dried blood spots to provide an additional sensitive functional biomarker of iodine status.

Global Iodine Nutrition: Where Do We Stand in 2013?

BACKGROUND Dietary iodine intake is required for the production of thyroid hormone. Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality. SUMMARY In 1990, the United Nations World Summit for Children established the goal of eliminating iodine deficiency worldwide. Considerable progress has since been achieved, largely through programs of universal salt iodization. Approximately 70% of all households worldwide currently have access to adequately iodized salt. In 2013, as defined by a national or subnational median urinary iodine concentration of 100-299 μg/L in school-aged children, 111 countries have sufficient iodine intake. Thirty countries remain iodine-deficient; 9 are moderately deficient, 21 are mildly deficient, and none are currently considered severely iodine-deficient. Ten countries have excessive iodine intake. In North America, both the United States and Canada are generally iodine-sufficient, although recent data suggest pregnant U.S. women are mildly iodine-deficient. Emerging issues include discrepancies between urinary iodine status in pregnant women compared to school-aged children in some populations, the problem of re-emerging iodine deficiency in parts of the developed world, the importance of food industry use of iodized salt, regions of iodine excess, and the potential effects of initiatives to lower population sodium consumption on iodine intake. CONCLUSIONS Although substantial progress has been made over the last several decades, iodine deficiency remains a significant health problem worldwide and affects both industrialized and developing nations. The ongoing monitoring of population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations, such as pregnant women and infants. There is also need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition. Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines.

The Impact of Iron and Selenium Deficiencies on Iodine and Thyroid Metabolism: Biochemistry and Relevance to Public Health

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.

Iodine supplementation of pregnant women in Europe: a review and recommendations

Objective: Nearly two-thirds of the population of Western and Central Europe live in countries that are iodine deficient. Damage to reproductive function and to the development of the fetus and newborn is the most important consequence of iodine deficiency. The objective of this review was to examine the iodine status of pregnant women in Europe and the potential need for iodine supplementation.Design: A MEDLINE/PubMed search and compilation of all published studies since 1990 of iodine nutrition and iodine supplementation of pregnant women in Europe, as well as an Internet-based search and review on availability and legislation of iodine supplements in the European Union.Results: Although the data suggest most women in Europe are iodine deficient during pregnancy, less than 50% receive supplementation with iodine. Mild-to-moderate iodine deficiency during pregnancy adversely affects thyroid function of the mother and newborn and mental development of the offspring and these adverse effects can be prevented or minimized by supplementation. There are no published data on the effect of iodine supplementation on long-term maternal and child outcomes. The iodine content of prenatal supplements in Europe varies widely; many commonly used products contain no iodine. The European Union is developing legislation to establish permissible levels for iodine in food supplements.Conclusions: In most European countries, pregnant women and women planning a pregnancy should receive an iodine-containing supplement (≈150 μg/day). Kelp and seaweed-based products, because of unacceptable variability in their iodine content, should be avoided. Prenatal supplement manufacturers should be encouraged to include adequate iodine in their products. Professional organizations should influence evolving EU legislation to ensure optimal doses for iodine in prenatal vitamin–mineral supplements.Sponsorship: International Council for Control of Iodine Deficiency Disorders.