Macronutrients as sources of food energy.

This background paper considers the extent to which the development of new recommendations for dietary energy requirements needs to account for the macronutrient (fat, carbohydrate, protein and alcohol) profiles of different diets. The issues are discussed from the dual perspectives of avoiding under-nutrition and obesity. It is shown that, in practice, human metabolic processes can adapt to a wide range of fuel supply by altering fuel selection. It is concluded that, at the metabolic level, only diets with the most extreme macronutrient composition would have any consequences by exceeding the natural ability to modify fuel selection. However, diets of different macronutrient composition and energy density can have profound implications for innate appetite regulation and hence overall energy consumption

FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. STUDY DESIGN AND METHODOLOGY: Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. RESULTS: FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=-0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=-0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =-0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=-2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=-0.36 (0.10), P=0.0007, haemoglobin = -1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). CONCLUSIONS: Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration

Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults.

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed

Tackling the triple threats of childhood malnutrition.

The term 'double burden of malnutrition' is usually interpreted in terms of the physical status of children: stunted and wasted children on the one hand and overweight/obese children on the other. There is a third category of malnutrition that can occur at either end of the anthropometric spectrum or, indeed, in children whose physical size may be close to ideal. This third type is most commonly articulated with the phrase 'hidden hunger' and is often illustrated by micronutrient deficiencies; thus, we refer to it here as 'undernutrition'. As understanding of such issues advances, we realise that there is a myriad of factors that may be influencing a child's road to nutritional health. In this BMC Medicine article collection we consider these influences and the impact they have, such as: the state of the child's environment; the effect this has on their risk of, and responses to, infection and on their gut; the consequences of poor nutrition on cognition and brain development; the key drivers of the obesity epidemic across the globe; and how undernourishment can affect a child's body composition. This collection showcases recent advances in the field, but likewise highlights ongoing challenges in the battle to achieve adequate nutrition for children across the globe

Helicobacter pylori infection and circulating ghrelin levels - a systematic review.

BACKGROUND: The nature of the association between ghrelin, an orexigenic hormone produced mainly in the stomach, and Helicobacter pylori (H pylori), a bacterium that colonises the stomach, is still controversial. We examined available evidence to determine whether an association exists between the two; and if one exists, in what direction. METHODS: We reviewed original English language studies on humans reporting circulating ghrelin levels in H pylori infected and un-infected participants; and circulating ghrelin levels before and after H pylori eradication. Meta-analyses were conducted for eligible studies by combining study specific estimates using the inverse variance method with weighted average for continuous outcomes in a random effects model. RESULTS: Seventeen out of 27 papers that reported ghrelin levels in H pylori positive and negative subjects found lower circulating ghrelin levels in H pylori positive subjects; while 10 found no difference. A meta-analysis of 19 studies with a total of 1801 participants showed a significantly higher circulating ghrelin concentration in H pylori negative participants than in H pylori positive participants (Effect estimate (95%CI) = -0.48 (-0.60, -0.36)). However, eradicating H pylori did not have any significant effect on circulating ghrelin levels (Effect estimate (95% CI) = 0.08 (-0.33, 0.16); Test for overall effect: Z = 0.67 (P = 0.5)). CONCLUSIONS: We conclude that circulating ghrelin levels are lower in H pylori infected people compared to those not infected; but the relationship between circulating ghrelin and eradication of H pylori is more complex

The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates.

Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates from non-tuberculous pathogens, but no biological mechanism to explain such effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial protection via a hepcidin-mediated hypoferraemia, limiting iron availability for pathogens. To test this we conducted a trial in 120 Gambian neonates comparing iron status in the first 5-days of life after allocation to: (1) All routine vaccinations at birth (BCG/Oral Polio Vaccine (OPV)/Hepatitis B Vaccine (HBV)); (2) BCG delayed until after the study period (at day 5); and (3) All routine vaccinations delayed until after the study period. Vaccine regime at birth did not significantly impact on any measured parameter of iron metabolism. However, the ability to detect an effect of BCG on iron metabolism may have been limited by short follow-up time and high activation of the inflammatory-iron axis in the study population

Reducing anaemia in low income countries: control of infection is essential.

In settings with high infection burdens, iron interventions for anaemia may be neither safe nor effective. Strategies to tackle the global burden of anaemia must take this into account, argue Sant-Rayn Pasricha and colleagues

Growth faltering in low-income countries.

Meta-analysis of growth data from over 50 low and low-middle income countries shows a consistent pattern of stunting and poor weight gain from about 3 months of age and persisting until at least 5 years. Children tend not to be wasted because their short stature offsets their underweight, leading to a rather adequately proportioned appearance. This frequently conceals the true levels of malnutrition in communities. At the macro-environmental level such growth faltering is due to the combined effects of poverty, food insecurity, low-dietary diversity, a highly infectious environment, poor washing facilities and poor understanding of the principles of nutrition and hygiene. These tend to be ameliorated as communities pass through the demographic transition with improved incomes and education. Because such changes will take generations to achieve, the global health community continues to search for effective interim solutions. Disappointingly, apart from intensive feeding programmes aimed at rehabilitating severely malnourished children, there are few examples of very successful nutrition interventions. This emphasizes the need for a better understanding of the etiology of growth failure. This paper uses anthropometric data collected over 6 decades in subsistence-farming communities from rural Gambia to illustrate the typical key features of growth faltering. Arising from this analysis, and from gaps in the published literature, the following issues are highlighted as still requiring a better resolution: (1) the pre-natal and inter-generational influences on growth failure; (2) the ontogeny of the infant immune system; (3) the exact nature of the precipitating insults that initiate gastroenteropathy; (4) the effects of both enteric and systemic infections on the hormonal regulation of growth; (5) interactions between macro- and micro-nutrient deficiencies and infections in causing growth failure, and (6) the role of the microbiome in modulating dietary influences on health and growth