Susan J. Fairweather-Tait

Selenium in Human Health and Disease

This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

Methods of assessment of iodine status in humans: a systematic review

BACKGROUND Zinc is an essential micronutrient for human health and has numerous structural and biochemical roles. The search for a reliable, sensitive, and specific index of zinc status has been the subject of considerable research, which has resulted in the identification of a number of potentially useful biomarkers. OBJECTIVE The objective was to assess the usefulness of biomarkers of zinc status in humans. DESIGN The methods included a structured search strategy using Ovid MEDLINE, EMBASE (Ovid), and the Cochrane Library CENTRAL databases; formal inclusion and exclusion criteria; data extraction into an Access database; quality and validity assessment; and meta-analysis. RESULTS Data on 32 potential biomarkers from 46 publications were analyzed. Plasma zinc concentration responded in a dose-dependent manner to dietary manipulation in adults, women, men, pregnant and lactating women, the elderly, and those at low and moderate baseline zinc status. Urinary zinc excretion responded to zinc status overall and in all subgroups for which there were sufficient data. Hair zinc concentration also responded, but there were insufficient studies for subgroup analysis. Platelet, polymorphonuclear cell, mononuclear cell, and erythrocyte zinc concentration and alkaline phosphatase activity did not appear to be effective biomarkers of zinc status. CONCLUSIONS This systematic review confirms that in healthy individuals, plasma, urinary, and hair zinc are reliable biomarkers of zinc status. Further high-quality studies using these biomarkers are required, particularly in infants, adolescents, and immigrant population groups for whom there are limited data. Studies are also required to fully assess a range of additional potential zinc biomarkers.

Ageing of the human metaorganism: the microbial counterpart

Human beings have been recently reviewed as ‘metaorganisms’ as a result of a close symbiotic relationship with the intestinal microbiota. This assumption imposes a more holistic view of the ageing process where dynamics of the interaction between environment, intestinal microbiota and host must be taken into consideration. Age-related physiological changes in the gastrointestinal tract, as well as modification in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbial ecosystem. Here we review the current knowledge of the changes occurring in the gut microbiota of old people, especially in the light of the most recent applications of the modern molecular characterisation techniques. The hypothetical involvement of the age-related gut microbiota unbalances in the inflamm-aging, and immunosenescence processes will also be discussed. Increasing evidence of the importance of the gut microbiota homeostasis for the host health has led to the consideration of medical/nutritional applications of this knowledge through the development of probiotic and prebiotic preparations specific for the aged population. The results of the few intervention trials reporting the use of pro/prebiotics in clinical conditions typical of the elderly will be critically reviewed.

Evidence of decreasing mineral density in wheat grain over the last 160 years.

Wheat is an important source of minerals such as iron, zinc, copper and magnesium in the UK diet. The dietary intake of these nutrients has fallen in recent years because of a combination of reduced energy requirements associated with sedentary lifestyles and changes in dietary patterns associated with lower micronutrient density in the diet. Recent publications using data from food composition tables indicate a downward trend in the mineral content of foods and it has been suggested that intensive farming practices may result in soil depletion of minerals. The aim of our study was to evaluate changes in the mineral concentration of wheat using a robust approach to establish whether trends are due to plant factors (e.g. cultivar, yield) or changes in soil nutrient concentration. The mineral concentration of archived wheat grain and soil samples from the Broadbalk Wheat Experiment (established in 1843 at Rothamsted, UK) was determined and trends over time examined in relation to cultivar, yield, and harvest index. The concentrations of zinc, iron, copper and magnesium remained stable between 1845 and the mid 1960s, but since then have decreased significantly, which coincided with the introduction of semi-dwarf, high-yielding cultivars. In comparison, the concentrations in soil have either increased or remained stable. Similarly decreasing trends were observed in different treatments receiving no fertilizers, inorganic fertilizers or organic manure. Multiple regression analysis showed that both increasing yield and harvest index were highly significant factors that explained the downward trend in grain mineral concentration.

Bioavailability of Minerals and Trace Elements

In this review a brief summary will be given of the food sources, absorptive mechanism and subsequent metabolism of the nine mineral and trace element identified as being nutritionally important (calcium, chromium, cuivre, iodine, iron, magnesium, manganese, selenium, zinc)

Selenium bioavailability: current knowledge and future research requirements

Information on selenium bioavailability is required to derive dietary recommendations and to evaluate and improve the quality of food products. The need for robust data is particularly important in light of recent suggestions of potential health benefits associated with different intakes of selenium. The issue is not straightforward, however, because of large variations in the selenium content of foods (determined by a combination of geologic/environmental factors and selenium supplementation of fertilizers and animal feedstuffs) and the chemical forms of the element, which are absorbed and metabolized differently. Although most dietary selenium is absorbed efficiently, the retention of organic forms is higher than that of inorganic forms. There are also complications in the assessment and quantification of selenium species within foodstuffs. Often, extraction is only partial, and the process can alter the form or forms present in the food. Efforts to improve, standardize, and make more widely available techniques for species quantification are required. Similarly, reliable and sensitive functional biomarkers of selenium status are required, together with improvements in current biomarker methods. This requirement is particularly important for the assessment of bioavailability, because some functional biomarkers respond differently to the various selenium species. The effect of genotype adds a potential further dimension to the process of deriving bioavailability estimates and underlines the need for further research to facilitate the process of deriving dietary recommendations in the future.

Interlaboratory trial on the determination of the In Vitro iron dialysability from food

An in vitro method for the estimation of iron bioavailability was subjected to an interlaboratory trial. The method involved a simulated gastrointestinal digestion using pepsin for the gastric stage followed by pancreatin and bile salts for the intestinal stage. The proportion of iron diffused through a semipermeable membrane (molecular mass cut-off 10 kDa) was used to measure the iron dialysability. An interlaboratory trial between nine laboratories was conducted to evaluate the repeatability and reproducibility of the agreed method. The reproducibility of the method among the participating laboratories was 20-30% and depended on the content of dialysable iron. Several factors contributing to the variation in the in vitro dialysability among laboratories are discussed. The pH adjustment in the intestinal digestion was identified as one of the critical parameters. The present in vitro method was used to evaluate the iron dialysability from three meals. The dialysability data were in reasonable agreement with human absorption data. The usefulness of the in vitro dialysability method is discussed.

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis.

BackgroundIn observational studies anaemia and iron deficiency are associated with cognitive deficits, suggesting that iron supplementation may improve cognitive function. However, due to the potential for confounding by socio-economic status in observational studies, this needs to be verified in data from randomised controlled trials (RCTs).AimTo assess whether iron supplementation improved cognitive domains: concentration, intelligence, memory, psychomotor skills and scholastic achievement.MethodologySearches included MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and bibliographies (to November 2008). Inclusion, data extraction and validity assessment were duplicated, and the meta-analysis used the standardised mean difference (SMD). Subgrouping, sensitivity analysis, assessment of publication bias and heterogeneity were employed.ResultsFourteen RCTs of children aged 6+, adolescents and women were included; no RCTs in men or older people were found. Iron supplementation improved attention and concentration irrespective of baseline iron status (SMD 0.59, 95% CI 0.29 to 0.90) without heterogeneity. In anaemic groups supplementation improved intelligence quotient (IQ) by 2.5 points (95% CI 1.24 to 3.76), but had no effect on non-anaemic participants, or on memory, psychomotor skills or scholastic achievement. However, the funnel plot suggested modest publication bias. The limited number of included studies were generally small, short and methodologically weak.ConclusionsThere was some evidence that iron supplementation improved attention, concentration and IQ, but this requires confirmation with well-powered, blinded, independently funded RCTs of at least one years duration in different age groups including children, adolescents, adults and older people, and across all levels of baseline iron status.

Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial

BACKGROUND Dietary recommendations for selenium differ between countries, mainly because of uncertainties over the definition of optimal selenium status. OBJECTIVE The objective was to examine the dose-response relations for different forms of selenium. DESIGN A randomized, double-blind, placebo-controlled dietary intervention was carried out in 119 healthy men and women aged 50-64 y living in the United Kingdom. Daily placebo or selenium-enriched yeast tablets containing 50, 100, or 200 microg Se ( approximately 60% selenomethionine), selenium-enriched onion meals ( approximately 66% gamma-glutamyl-methylselenocysteine, providing the equivalent of 50 microg Se/d), or unenriched onion meals were consumed for 12 wk. Changes in platelet glutathione peroxidase activity and in plasma selenium and selenoprotein P concentrations were measured. RESULTS The mean baseline plasma selenium concentration for all subjects was 95.7 +/- 11.5 ng/mL, which increased significantly by 10 wk to steady state concentrations of 118.3 +/- 13.1, 152.0 +/- 24.3, and 177.4 +/- 26.3 ng/mL in those who consumed 50, 100, or 200 microg Se-yeast/d, respectively. Platelet glutathione peroxidase activity did not change significantly in response to either dose or form of selenium. Selenoprotein P increased significantly in all selenium intervention groups from an overall baseline mean of 4.99 +/- 0.80 microg/mL to 6.17 +/- 0.85, 6.73 +/- 1.01, 6.59 +/- 0.64, and 5.72 +/- 0.75 microg/mL in those who consumed 50, 100, or 200 microg Se-yeast/d and 50 microg Se-enriched onions/d, respectively. CONCLUSIONS Plasma selenoprotein P is a useful biomarker of status in populations with relatively low selenium intakes because it responds to different dietary forms of selenium. To optimize the plasma selenoprotein P concentration in this study, 50 microg Se/d was required in addition to the habitual intake of approximately 55 microg/d. In the context of established relations between plasma selenium and risk of cancer and mortality, and recognizing the important functions of selenoprotein P, these results provide important evidence for deriving estimated average requirements for selenium in adults. This trial was registered at clinicaltrials.gov as NCT00279812.