Harry J McArdle

Low-grade inflammation, diet composition and health: current research evidence and its translation.

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institutes European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Micronutrients in fetal growth and development

The roles that the different vitamins and minerals play in fetal growth and development are reviewed, primarily with respect to growth and differentiation in humans; but, as appropriate, data provided from animal and cellular studies are also considered.

Fetal iron status regulates maternal iron metabolism during pregnancy in the rat

Iron metabolism during pregnancy is biased toward maintaining the fetal supply, even at the cost of anemia in the mother. The mechanisms regulating this are not well understood. Here, we examine iron deficiency and supplementation on the hierarchy of iron supply and the gene expression of proteins that regulate iron metabolism in the rat. Dams were fed iron-deficient diets for 4 wk, mated, and either continued on the deficient diet or an iron-supplemented diet during either the first half or the second half of their pregnancy. A control group was maintained on normal iron throughout. They were killed at 0.5, 12.5, or 21.5 days of gestation, and tissues and blood samples were collected. Deficiency and supplementation had differential effects on maternal and fetal hematocrit and liver iron levels. From early in pregnancy, a hierarchy of iron supply is established benefiting the fetus to the detriment of the mother. Transferrin receptor, transferrin receptor 2, and hepcidin mRNA expression were regulated by both iron deficiency and supplementation. Expression patterns showed both organ and supplementation protocol dependence. Further analysis indicated that iron levels in the fetal, and not maternal, liver regulate the expression of liver transferrin receptor and hepcidin expression in the mother.

Dietary iron intake during early pregnancy and birth outcomes in a cohort of British women

BACKGROUND Iron deficiency during pregnancy is associated with adverse birth outcomes, particularly, if present during early gestation. Iron supplements are widely recommended during pregnancy, but evidence of their benefit in relation to infant outcomes is not established. This study was performed in the UK, where iron supplements are not routinely recommended during pregnancy, to investigate the association between iron intake in pregnancy and size at birth. METHODS From a prospective cohort of 1274 pregnant women aged 18–45 years, dietary intake was reported in a 24-h recall administered by a research midwife at 12-week gestation. Dietary supplement intake was ascertained using dietary recall and three questionnaires in the first, second and third trimesters. RESULTS Of the cohort of pregnant women, 80% reported dietary iron intake below the UK Reference Nutrient Intake of 14.8 mg/day. Those reported taking iron-containing supplements in the first, second and third trimesters were 24, 15 and 8%, respectively. Women with dietary iron intake >14.8 mg/day were more likely to be older, have a higher socioeconomic profile and take supplements during the first trimester. Vegetarians were less likely to have low dietary iron intake [odds ratio = 0.5, 95% confidence interval (CI): 0.4, 0.8] and more likely to take supplements during the first and second trimesters. Total iron intake, but not iron intake from food only, was associated with birthweight centile (adjusted change = 2.5 centiles/10 mg increase in iron, 95% CI: 0.4, 4.6). This association was stronger in the high vitamin C intake group, but effect modification was not significant. CONCLUSION There was a positive relationship between total iron intake, from food and supplements, in early pregnancy and birthweight. Iron intake, both from diet and supplements, during the first trimester of pregnancy was higher in vegetarians and women with a better socioeconomic profile.

Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health

Abstract EFSA asked the Panel on Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

A common cause for a common phenotype: the gatekeeper hypothesis in fetal programming

Sub-optimal nutrition during pregnancy has been shown to have long-term effects on the health of offspring in both humans and animals. The most common outcomes of such programming are hypertension, obesity, dyslipidaemia and insulin resistance. This spectrum of disorders, collectively known as metabolic syndrome, appears to be the consequence of nutritional insult during early development, irrespective of the nutritional stress experienced. For example, diets low in protein diet, high in fat, or deficient in iron are all associated with programming of cardiovascular and metabolic disorders when fed during rat pregnancy. In this paper, we hypothesise that the nutritional stresses act on genes or gene pathways common to all of the insults. We have termed these genes and/or gene pathways the “gatekeepers” and hence developed the “gatekeeper hypothesis”. In this paper, we examine the background to the hypothesis and postulate some possible mechanisms or pathways that may constitute programming gatekeepers.

Iron and copper in fetal development.

Copper and iron are both essential micronutrients. Because they can both accept and donate electrons, they are central to many energy dependent chemical reactions. For example, copper is a critical part of ferroxidase enzymes ceruloplasmin, hephaestin and zyklopen, as well as enzymes such as dopamine-β-monoxygenase, while iron is part of the catalytic site of many cytochromes and enzymes involved in fatty acid desaturation. Unsurprisingly, therefore, copper and iron deficiency, especially during pregnancy, when cell proliferation and differentiation are very active, sub-optimal nutrient status can lead to serious consequences. These problems can persist into adulthood, with an increased risk of mental problems such as schizophrenia and, in animal models at least, hypertension and obesity. In this review, we consider what these problems are and how they may arise. We examine the role of copper and iron deficiencies separately during fetal development, in terms of birth outcome and then how problems with status in utero can have long term sequelae for the offspring. We examine several possible mechanisms of action, both direct and indirect. Direct causes include, for example, reduced enzyme activity, while indirect ones may result from changes in cytokine activity, reductions in cell number or increased apoptosis, to name but a few. We examine a very important area of nutrition-interactions between the micronutrients and conclude that, while we have made significant advances in understanding the relationship between micronutrient status and pregnancy outcome, there is still much to be learned.

The Micronutrient Genomics Project: a community-driven knowledge base for micronutrient research.

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.

The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women

Please cite this paper as: Alwan N, Greenwood D, Simpson N, McArdle H, Cade J. The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women. BJOG 2010;117:821–829.

Fetal regulation of iron transport during pregnancy

During pregnancy, iron is transported from mother to fetus across the placenta. Iron is essential for many biological processes, including the transfer of oxygen in blood, but it can also be toxic. Elaborate and elegant mechanisms have evolved to make sure that the potential for oxidative damage is minimized. In this article, we examine how iron is transferred from the maternal liver to the placenta, taken up, and transferred to the fetal liver. We consider the molecular mechanisms and how they are regulated. In addition, we use data from previously published articles to examine how the processes are regulated and what adaptations can occur to ameliorate the consequences of iron deficiency--an all too common problem in pregnancy, even in the developed world. Finally, we examine some of the many questions that remain about the transfer process and consider how nutrients interact and what the consequences of these interactions may be for the mother and her developing infant.