Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated a link between status and disease activity with conflicting results. Variation with disease activity index measures used alongside methodological limitations within the study design may partially explain these findings. This review discusses the importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

Endothelial damage is central to the initiation and progression of atherosclerosis, while in addition vascular endothelial cells secrete several anti-atherogenic substances including the potent vasodilator nitric oxide. Increased adhesion molecule expression, in response to pathophysiological stimuli is perhaps the earliest indicator of compromised endothelial integrity. Obesity and adiposity are associated with an increased risk of CVD, influencing disease progression via a number of mechanisms, including enhanced endothelial activation. This review discusses possible mechanisms linking adiposity and more specifically regional fat depots with endothelial function and evaluates studies investigating the effect of weight loss on endothelial function, assessed by biochemical and physiological measurements. Overall, the research to date suggests that visceral adiposity is a stronger predictor of endothelial activation than overall adiposity, possibly mediated via the action of NEFA in circulation. While in general there is a suggestion that weight loss is associated with significant improvements in endothelial function, this is not apparent in all interventions and published literature to date provides less than convincing evidence for the effects of weight loss on endothelial activation.

Over a decade of intense research in the field of obesity has led to the knowledge that chronic, excessive adipose tissue expansion leads to an increase in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily thought to stem from the low-grade, systemic inflammatory response syndrome that characterises adipose tissue in obesity, and this itself is thought to arise from the complex interplay of factors including metabolic endotoxaemia, increased plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations of vitamins and antioxidants are lower in obese individuals than in the non-obese, which is hypothesised to negatively affect the development of inflammation and disease in obesity. This paper provides a review of the current literature investigating the potential of nutraceuticals to ameliorate the development of oxidative stress and inflammation in obesity, thereby limiting the onset of obesity complications. Research has found nutraceuticals able to positively modulate the activity of adipocyte cell lines and further positive effects have been found in other aspects of pathogenic obesity. While their ability to affect weight loss is still controversial, it is clear that they have a great potential to reverse the development of overweight and obesity-related comorbidities; this, however, still requires much research especially that utilising well-structured randomised controlled trials.

Obesity is a public health concern worldwide, arising from multifaceted and complex causes that relate to individual choice and lifestyle, and the influences of wider society. In addition to a long-standing focus on both childhood and adult obesity, there has been more recent concern relating to maternal obesity. This review explores the published evidence relating to maternal obesity incidence and associated inequalities, the impact of obesity on maternity services, and associated guidelines. Epidemiological data comprising three national maternal obesity datasets within the UK have identified a significant increase in maternal obesity in recent years, and reflect broad socio-demographic inequalities particularly deprivation, ethnicity and unemployment. Obese pregnancies present increased risk of complications that require more resource intensive antenatal and perinatal care, such as caesarean deliveries, gestational diabetes, haemorrhage, infections and congenital anomalies. Healthcare professionals also face difficulties when managing the care of women in pregnancy as obesity is an emotive and stigmatising topic. There is a lack of good-quality evidence for effective interventions to tackle maternal obesity. Recently published national guidelines for the clinical management and weight management of maternal obesity offer advice for professionals, but acknowledge the limitations of the evidence base. The consequence of these difficulties is an absence of support services available for women. Further evaluative research is thus required to assess the effectiveness of interventions with women before, during and after pregnancy. Qualitative work with women will also be needed to help inform the development of more sensitive risk communication and women-centred services.

The prevalence of obesity in pregnancy is rising exponentially; about 15–20% of pregnant women now enter pregnancy with a BMI which would define them as obese. This paper provides a review of the strong links between obesity and adverse pregnancy outcome which operate across a range of pregnancy complications. For example, obesity is associated with an increased risk of maternal mortality, gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum haemorrhage. Obesity also complicates operative delivery; it makes operative delivery more difficult, increases complications and paradoxically increases the need for operative delivery. The risk of the majority of these complications is amplified by excess weight gain in pregnancy and increases in proportion to the degree of obesity, for example, women with extreme obesity have OR of 7·89 for gestational diabetes and 3·84 for postpartum haemorrhage compared to their lean counterparts. The consequences of maternal obesity do not stop once the baby is born. Maternal obesity programmes a variety of long-term adverse outcomes, including obesity in the offspring at adulthood. Such an effect is mediated at least in part via high birthweight; a recent study has suggested that the odds of adult obesity are two-fold greater in babies weighing more than 4 kg at birth. The mechanism by which obesity causes adverse pregnancy outcome is uncertain. This paper reviews the emerging evidence that hyperglycaemia and insulin resistance may both play a role: the links between hyperglycaemia in pregnancy and both increased birthweight and insulin resistance have been demonstrated in two large studies. Lastly, we discuss the nature and rationale for possible intervention strategies in obese pregnant women.

The global pandemic of maternal obesity presents a major challenge for healthcare providers, and has significant short- and long-term implications for both maternal and fetal health. Currently, the evidence-base underpinning many of the interventions either currently in use or recommended to improve pregnancy outcome in obese women is limited. The nature and timing of these interventions vary widely, ranging from simple advice to more intensive dietary and exercise programmes, cognitive behavioural therapy and drug trials. In addition, a growing number of very severely obese women now enter pregnancy having had surgical interventions. Although surgical interventions such as gastric bypass or banding may be associated with improved pregnancy outcomes, these women have particular nutritional requirements, which need to be addressed to optimise pregnancy outcome. Until the outcomes of ongoing current trials are reported and provide a firm evidence base on which to base future intervention strategies and guide evidence based care for obese pregnant women, pregnancy outcome is best optimised by high-risk antenatal care delivered by healthcare providers who are experienced in supporting these high-risk women.

Over the past several decades, the incidence of atopic diseases such as asthma, atopic dermatitis and food allergies has increased dramatically. Although atopic diseases have a clear genetic basis, environmental factors, including early infant nutrition, may have an important influence on their development. Therefore, attempts have been made to reduce the risk of the development of allergy using dietary modifications, mainly focused on longer breast-feeding and delayed introduction or elimination of foods identified as potentially most allergenic. Recently, there is also an increasing interest in the active prevention of atopy using specific dietary components. Many studies have shown that breast-feeding may have the protective effect against future atopic dermatitis and early childhood wheezing. Concerning complementary feeding, there is evidence that the introduction of complementary foods before 4 months of age may increase the risk for atopic dermatitis. However, there is no current convincing evidence that delaying introduction of solids after 6 months of age has a significant protective effect on the development of atopic disease regardless of whether infants are fed cow's milk protein formula or human subject's milk, and this includes delaying the introduction of foods that are considered to be highly allergic, such as fish, eggs and foods containing peanut protein. In conclusion, as early nutrition may have profound implications for long-term health and atopy later in life, it presents an opportunity to prevent or delay the onset of atopic diseases.

The relationship between breast-feeding and later cardiovascular health has been investigated in randomised trials and observational studies. This review focuses on randomised control trials, regarded as the ‘gold standard’ in establishing causal relationships between interventions and outcomes. Since it is not ethical to randomise healthy term infants to be breast- or formula-fed, only two randomised control trials have examined effects of breast-feeding on later health. In one randomised control trial, preterm infants randomised to receive banked donor breast milk had significantly lower blood pressure (BP), more favourable plasma lipid profile and reduced leptin resistance at age of 13–15 years compared with those who were fed preterm formula; with a dose–response relationship between the proportion of human milk and later outcomes. In contrast, a cluster-randomised control trial of a breast-feeding promotion intervention in healthy term infants (Promotion of Breast-feeding Intervention Trial study) found no effect of the intervention on adiposity or BP at 6 years, despite increased incidence, duration and exclusivity of breast-feeding. Potential explanations for the discrepancy between the two studies include: (i) beneficial effects of breast milk on cardiovascular health might be confined to preterm infants; (ii) effects on cardiovascular outcomes may not manifest until adolescence, a concept supported by other studies; (iii) if the underlying mechanism for the effect of breast-feeding on later cardiovascular outcome is slower early growth; a concept supported by data from animal models, human observational studies and now experimental studies in human subjects; it is plausible that differences in early growth between groups in the Promotion of Breast-feeding Intervention Trial were insufficient to produce a detectable effect on these outcomes.

This paper considers the body of observational evidence examining the association of being breast-fed to cardiovascular risk factors and outcomes in later life, and whether any potentially advantageous findings are causal. Early cardiovascular consequences/correlates of breast-feeding, compared to being formula fed, include markedly higher levels of total blood cholesterol, lower levels of pre-prandial blood glucose and insulin and lower levels of adiposity. However, a key issue is whether these early differences at a period of rapid development programme/influence cardiovascular risk factors and outcomes in later life. Evidence of long-term effects of early feeding, largely from observational studies, has shown that those breast-fed have lower levels of blood total cholesterol, lower risk of type-2 diabetes and marginally lower levels of adiposity and blood pressure in adult life. There is no strong evidence to suggest effects of early feeding on adult levels of blood glucose, blood insulin and CHD outcomes, although further data are needed. However, the influence of confounding factors, such as maternal body size, maternal smoking and socio-demographic factors, and exclusivity of early feeding on these potentially beneficial associations needs to be considered before inferring any causal effects. Moreover, fewer studies have examined whether duration of exclusive breast-feeding has a graded influence on these risk factors and outcomes; such data would help further in deciding upon causal associations. While strong observational evidence suggests nutritional programming of adult cholesterol levels, associations with other markers of cardiometabolic risk and their consequences in later life need to be confirmed in well-conducted observational and experimental studies.

An understanding of how infant eating behaviour relates to later obesity is required if interventions in infancy are to be attempted. The aim of this paper is to review findings from the Gateshead Millennium Study to describe (i) what we have already established about the relationship between infant feeding transitions, infancy weight gain and eating behaviour and (ii) describe new analyses that examine how infant eating behaviour and temperament relate to infancy weight gain and childhood adiposity. The Gateshead Millennium Study recruited 1029 infants at birth and parents completed questionnaires five times in the first year. We have already described how starting solids and ceasing breast-feeding seems to be a response to rapid early weight gain, rather than a cause, and that parents identify and respond to the individual appetite characteristics of their child. A number of questions about eating behaviour at 12 months were used to construct an infancy eating avidity score that was positively associated with height at age 7–8 years, but not with an adiposity index constructed using bioelectrical impedance, waist and skinfolds. Infancy eating avidity score was associated with greater fussiness and lower satiety responsivity on the Child Eating Behaviour Questionnaire at age 6–8 years. Temperament measured at age 6 weeks and 8 months showed no consistent associations with either infancy weight gain or adiposity at 6–8 years. While infancy may seem a logical time to intervene with children at risk of future obesity, the collective findings from this substantial population-based study largely suggest otherwise.

Therapy of choice in obese children and adolescents is lifestyle intervention based on nutrition education, behavioural treatment and exercise treatment. Its efficacy even after the end of intervention has been proven by several randomised-controlled trials and meta-analyses including a recent Cochrane review. However, randomised-controlled trials are likely to overestimate the effectiveness. Studies under normal day-to-day circumstances demonstrated only a very moderate effect on weight loss (<10% success rate 2 years after the onset of intervention). A reduction of >0·5 SDS-BMI (which means a stable weight over 1 year in growing children) is associated with an improvement of cardiovascular risk factors, while improvements of quality of life seem independent of the degree of weight loss. Younger children and less overweight children particularly profit from lifestyle interventions in contrast to extremely obese adolescents. Recent studies demonstrated that involving parents is crucial for success, suggesting that parents and children and not children alone should be the primary target of interventions. Failures in weight reduction are attributed not only to a lack of motivation but also to other aspects particular to the genetic background. The techniques, more than the contents, of an intervention influence the treatment outcome. Besides behavioural therapy, systemic and solution-focused treatments are important. Future longitudinal research should focus on the identification of which children and adolescents profit from which kind of intervention, in order to be able to tailor specific treatment approaches. Studies under normal day-to-day circumstances are necessary to prove the benefit of this kind of intervention.

The recent rise in the prevalence of obesity in the UK population includes women of reproductive age and children. For both groups there are specific health concerns consequent on excess bodyweight, including obstetric complications, fetal growth abnormalities and a range of obesity co-morbidities seen in children that were rarely found in young people a generation earlier. This paper identifies some of the issues which challenge policy-makers: guidelines for gestational weight gain and for weight loss after pregnancy; inequalities and interventions in pregnancy; interventions to prevent child obesity; and the role of individuals, government and the commercial sector in implementing policies for promoting healthy weight.