The objective of the present review is to provide an overview of the metabolic effects of pro-inflammatory cytokine production during infection and injury; to highlight the disadvantages of pro-inflammatory cytokine production and inflammatory stress on morbidity and mortality of patients; to identify the influence of genetics and adiposity on inflammatory stress in patients and to indicate how nutrients may modulate the inflammatory response in patients. Recent research has shown clearly that adipose tissue actively secretes a wide range of pro- and anti-inflammatory cytokines. Paradoxically, although inflammation is an essential part of the response of the body to infection, surgery and trauma, it can adversely affect patient outcome. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidaemia, muscle protein loss and oxidant stress. These effects, as well as being present during infective disease, are also present in diseases with a covert inflammatory basis. These latter diseases include obesity and type 2 diabetes mellitus. Inflammatory stress also increases during aging. The level of cytokine production, within individuals, is influenced by single nucleotide polymorphisms (SNP) in cytokine genes. The combination of SNP controls the relative level of inflammatory stress in both overt and covert inflammatory diseases. The impact of cytokine genotype on the intensity of inflammatory stress derived from an obese state is unknown. While studies remain to be done in the latter context, evidence shows that these genomic characteristics influence morbidity and mortality in infectious disease and diseases with an underlying inflammatory basis and thereby influence the cost of in-patient obesity. Antioxidants and n-3 PUFA alter the intensity of the inflammatory process. Recent studies show that genotypic factors influence the effectiveness of immunonutrients. A better understanding of this aspect of nutrient–gene interactions and of the genomic factors that influence the intensity of inflammation during disease will help in the more effective targeting of nutritional therapy.

Excess energy intake and positive energy balance are associated with the development of obesity and insulin resistance, which is a key feature underlying the pathophysiology of type 2 diabetes. It is possible that dietary macronutrient intake may also be important, in particular increased levels of sugar and fat. High-fat energy-dense diets contribute to energy excess and obesity. Fat type is also a factor, with evidence suggesting that saturated fat intake is linked to insulin resistance. However, controversy exists about the role of carbohydrate in the development of diabetes. Epidemiological studies suggest that the risk of diabetes is unrelated to the total amount of carbohydrate, but that fibre intake and glycaemic load are important. Common dietary advice for the prevention of diabetes often advocates complex carbohydrates and restriction of simple carbohydrates; however, sugars may not be the main contributor to glycaemic load. Evidence continues to emerge in relation to the influence of dietary sugars intake on insulin resistance. In broader dietary terms fruit and vegetable intake may influence insulin resistance, possibly related to increased intake of fibre and micronutrients or displacement of other food types. There is also considerable debate about the most effective diet and appropriate macronutrient composition to facilitate weight loss. Recent evidence suggests comparable effects of diets with varying macronutrient profiles on weight loss, which is predominantly related to energy restriction. However, based on the results of diabetes prevention trials focusing on lifestyle measures, evidence favours low-fat diets as the preferred approach for weight loss and diabetes prevention.

Meta- and mega-analysis of randomised controlled trials indicate reduction in tender joint counts and decreased use of non-steroidal anti-inflammatory drugs with fish-oil supplementation in long-standing rheumatoid arthritis (RA). Since non-steroidal anti-inflammatory drugs confer cardiovascular risk and there is increased cardiovascular mortality in RA, an additional benefit of fish oil in RA may be reduced cardiovascular risk via direct mechanisms and decreased non-steroidal anti-inflammatory drug use. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and provision of substrates for synthesis of lipid suppressors of inflammation (resolvins). Future studies need progress in clinical trial design and need to shift from long-standing disease to examination of recent-onset RA. We are addressing these issues in a current randomised controlled trial of fish oil in recent-onset RA, where the aim is to intervene before joint damage has occurred. Unlike previous studies, the trial occurs on a background of drug regimens determined by an algorithm that is responsive to disease activity and drug intolerance. This allows drug use to be an outcome measure whereas in previous trial designs, clinical need to alter drug use was a ‘problem’. Despite evidence for efficacy and plausible biological mechanisms, the limited clinical use of fish oil indicates there are barriers to its use. These probably include the pharmaceutical dominance of RA therapies and the perception that fish oil has relatively modest effects. However, when collateral benefits of fish oil are included within efficacy, the argument for its adjunctive use in RA is strong.

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate pro-survival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects.

The worldwide obesity epidemic over the last 20 years has led to a dramatic increase in the prevalence of non-alcoholic fatty liver disease, the hepatic manifestation of the metabolic syndrome. Estimates of prevalence vary depending on the population studied and the methods used to assess hepatic fat content, but are commonly quoted as between 10 and 30% of the adults in the Western hemisphere. Fatty liver develops when fatty acid uptake and synthesis in the liver exceeds fatty acid oxidation and export as TAG. Studies of pathogenesis point to insulin resistance, lipotoxicity, oxidative stress and chronic inflammation being central to the development and progression of the disease. A proportion of individuals with fatty liver develop progressive disease, though large prospective longitudinal studies are lacking. Nevertheless, fatty liver is associated with increased all-cause and liver-related mortality compared with the general population. Management of fatty liver centres around lifestyle and dietary measures to induce controlled and sustained weight loss. Management of cardiovascular risk factors aims to reduce mortality, while certain dietary interventions have been shown to reduce steatosis and inflammation. Specific pharmacological treatments also show promise, but their use is not widespread. A multi-system and multi-disciplinary approach to the management of this disorder is proposed.

Obesity is a rapidly-growing public health problem that is related in part to the foods available in the eating environment. Properties of foods such as portion size and energy density (kJ/g) have robust effects on energy intake; large portions of energy-dense foods promote excess consumption and this effect starts in early childhood. Studies show, however, that in both adults and children these food characteristics can also be used strategically to moderate energy intake, as well as to improve diet quality. Dietary energy density can be reduced by increasing intake of water-rich foods such as vegetables and fruits. Their high water content allows individuals to eat satisfying portions of food while decreasing energy intake. Filling up at the start of a meal with vegetables or fruit and increasing the proportion of vegetables in a main course have been found to control hunger and moderate energy intake. Data from several clinical trials have also demonstrated that reducing dietary energy density by the addition of water-rich foods is associated with substantial weight loss even though participants eat greater amounts of food. Population-based assessments indicate that beginning in childhood there is a relationship between consuming large portions of energy-dense foods and obesity. These data suggest that the promotion of diets that are reduced in energy density should be an important component of future efforts to both prevent and treat obesity.

Successfully tackling obesity is a long-term commitment. Current levels of obesity in the population have been ≥30 years in the making. Not only will this position take time to reverse but there will be a considerable time lag before health and economic benefits are achieved through reductions in the morbidity from obesity-related diseases. There is clear evidence that policies aimed only at individuals will be inadequate and that increasing small-scale interventions will not suffice. Major action to prevent excess weight gain at a population level is required. The Foresight Report has confirmed that a ‘whole system’ approach is critical. This approach will require a broad portfolio of integrated policy responses including both national and local measures. This strategy requires action by government, both central and local, industry and communities and by families and the societies in which they live.