Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case–control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B12, raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individual-patient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.

The involvement of free radicals and reactive oxygen and nitrogen species in the pathology of inflammatory and degenerative disease has been widely accepted, although the centrality of these species to the outcome of these diseases is still a matter for debate. In the case of CVD, and particularly the development of the atherosclerotic plaque, the oxidation of LDL is of particular importance and appears to explain many of the events that occur during the life history of the plaque. The corollary of this situation is that antioxidants must be a benign force to protect the population from the modern scourge of heart disease. In fact, recent evidence from intervention studies with large doses of the antioxidant vitamins and other antioxidants in foods has been very disappointing. Here, the background for the belief that antioxidants ought to be beneficial is examined and an attempt made to explain why the results of these intervention studies have been unsuccessful. It is agreed that a diet rich in fruit and vegetables is protective for both CVD and cancer, but the explanation for this effect may not necessarily lie with the presence of antioxidants.

Metabolomics aims to profile all small molecules that are present in biological samples such as biofluids, tissue extracts and culture media. Combining the data obtained with multivariate data analysis tools allows the exploration of changes induced by a biological treatment or changes resulting from phenotype. Recently, there has been a large increase in interest in using metabolomics in nutritional research and because of the intimate relationship between nutrients and metabolism there exists great potential for the use of metabolomics within nutritional research. However, for metabolomics to reach its full potential within this field it is also important to be realistic about the challenges that are faced. Examples of such challenges include the necessity to have a clear understanding of the causes of variation in human metabolomic profiles, the effects of the gut microflora on the metabolomic profile and the interaction of the gut microflora with the host's metabolism. A further challenge that is particularly relevant for human nutritional research is the difficulty associated with biological interpretation of the data. Notwithstanding these and other challenges, several examples of successful applications to nutritional research exist. The link between the human metabolic phenotype, as characterised by metabolomic profiles, and dietary preferences proposes the potential role of metabolomics in personalised nutrition.

Prevalence of obesity in preschool children has increased dramatically in recent years. The preschool years (age 3–6 years) have been regarded as critical for the programming of energy balance, via the concept of early ‘adiposity rebound’. Children who undergo early adiposity rebound are at increased risk of later obesity. Recent evidence suggests that associations between timing of adiposity rebound and later obesity may not reflect programming, but might denote that ‘obesogenic’ growth trajectories are often established by the preschool period. Studies of objectively-measured physical activity and sedentary behaviour in preschool children show that levels of physical activity are typically low and sedentary behaviour high. The review of evidence presented here is supportive of the hypothesis that physical activity is protective against obesity in the preschool period, and that sedentary behaviour, particularly television viewing, is obesogenic. Definitive evidence on dose–response relationships between physical activity, sedentary behaviour and obesity remain unclear. Dose–response evidence could be obtained fairly readily by intervention and longitudinal observational studies that use accelerometry in preschool children. The generalisability of much of the evidence base is limited and there is a need for research on the influence of physical activity and sedentary behaviour in the preschool years in the aetiology of obesity in the developing world.

Whereas common infectious and parasitic diseases such as malaria and the HIV/AIDS pandemic remain major unresolved health problems in many developing countries, emerging non-communicable diseases relating to diet and lifestyle have been increasing over the last two decades, thus creating a double burden of disease and impacting negatively on already over-stretched health services in these countries. Prevalence rates for type 2 diabetes mellitus and CVD in sub-Saharan Africa have seen a 10-fold increase in the last 20 years. In the Arab Gulf current prevalence rates are between 25 and 35% for the adult population, whilst evidence of the metabolic syndrome is emerging in children and adolescents. The present review focuses on the concept of the epidemiological and nutritional transition. It looks at historical trends in socio-economic status and lifestyle and trends in nutrition-related non-communicable diseases over the last two decades, particularly in developing countries with rising income levels, as well as the other extreme of poverty, chronic hunger and coping strategies and metabolic adaptations in fetal life that predispose to non-communicable disease risk in later life. The role of preventable environmental risk factors for obesity and the metabolic syndrome in developing countries is emphasized and also these challenges are related to meeting the millennium development goals. The possible implications of these changing trends for human and economic development in poorly-resourced healthcare settings and the implications for nutrition training are also discussed.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.

Morphological and immunocytochemical studies have elucidated the complex processes involved in atherogenesis. The notion of plaque instability has emerged from this work and underscored the importance of inflammation in determining clinical complications associated with atherosclerosis, such as acute coronary syndrome. Cells of the immune system have been detected within atherosclerotic lesions and auto-antibodies directed against modified LDL and heat-shock proteins have been identified in the blood of individuals with atherosclerosis. The use of risk ‘engines’, e.g. the Framingham coronary risk score, has facilitated the identification of individuals at high risk, but the constituent classical risk factors used in these algorithms do not adequately differentiate individuals at moderate risk. As age is a major component of the equations used in these algorithms they are not particularly useful in young adults, and their applicability to non-Caucasian populations has been questioned. Biomarkers of early disease and plaque instability have therefore both been sought. Although some of these markers have been shown individually to be associated with a significant hazard ratio, no substantial improvement in discrimination has been demonstrated when they are incorporated into a risk ‘engine’. The latter has generally been assessed by receiver operator characteristic curve analysis, although this approach has been criticised. Other modalities, including imaging and functional assessments of vascular function, are now being developed for clinical use.

UNICEF has stated that urban poverty is primarily found in squatter settlements. At present 13·5% of all South African households live in informal settlements. The major research question is to what extent does poverty influence the food, nutrition and health of informal-settlement dwellers. The purpose of the present study was to determine the depth of poverty in this community and to measure the possible effect that planned food and nutrition interventions may have on eliminating poverty in this area. Pre-tested questionnaires were administered to 340 randomly-selected caregivers. A validated quantified FFQ was administered by trained enumerators as the test measurement for dietary intake and food consumption patterns and 24 h recall was used as the reference measurement, and the data were analysed. A poverty model was used to measure the impact of extra income on the poverty levels of 190 households. Of the respondents 89% lived in Zn shacks and the average household size was 4·9 individuals. The unemployment rate was 94·2% for respondents and 64·9% for their partners. The majority of households (68·8%) had an income of <R 500 (£35) per month and 58·3% spent <R 100 (£6·90) per week on food. The average poverty gap was R 1342·21 (£93) and the poverty gap ratio was 56%. The poverty model showed that an increase of R 500 (£35) in monthly household income results in a poverty gap ratio of 35%. The poverty model confirmed that the impact of food and nutrition interventions on poverty can be measured and that when planning these interventions the model could be used to measure their feasibility. The results indicate that this community is poverty-stricken and has chronic food insecurity, and they will be used to facilitate planning and implementation of sustainable income-generating community-based interventions to promote urban food security and alleviate poverty in this community.