In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

Alterations in intestinal microbiota composition and function have been linked to conditions including functional gastrointestinal disorders, obesity and diabetes. The gut microbiome encodes metabolic capability in excess of that encoded by the human genome, and bacterially produced enzymes are important for releasing nutrients from complex dietary ingredients. Previous culture-based studies had indicated that the gut microbiota of older people was different from that of younger adults, but the detailed findings were contradictory. Small-scale studies had also shown that the microbiota composition could be altered by dietary intervention or supplementation. We showed that the core microbiota and aggregate composition in 161 seniors was distinct from that of younger persons. To further investigate the reasons for this variation, we analysed the microbiota composition of 178 elderly subjects for whom the dietary intake data were available. The data revealed distinct microbiota composition groups, which overlapped with distinct dietary patterns that were governed by where people lived: at home, in rehabilitation or in long-term residential care. These diet–microbiota separations correlated with cluster analysis of NMR-derived faecal metabolites and shotgun metagenomic data. Major separations in the microbiota correlated with selected clinical measurements. It should thus be possible to programme the microbiota to enrich bacterial species and activities that promote healthier ageing. A number of other studies have investigated the effect of certain dietary components and their ability to modulate the microbiota composition to promote health. This review will discuss dietary interventions conducted thus far, especially those in elderly populations and highlight their impact on the intestinal microbiota.

The immune response promotes a complex series of reactions by the host in an effort to prevent ongoing tissue damage, isolate and destroy the infective organism and activate the repair processes that are necessary for restoring normal function. The homoeostatic process is known as inflammation and the early set of reactions that are induced are known as the acute phase response (APR). The APR has marked effects on the circulation, metabolism in the liver and the plasma concentration of many nutrients. The changes in nutrient concentrations follow a cyclic pattern; occurring before any clinical evidence of disease, being at their most pronounced during the disease and remaining in convalescence when all evidence of disease or trauma has disappeared. Therefore, where susceptibility to disease is high as in people who are HIV+ but still apparently healthy, obtaining an accurate measurement of nutritional status may not be possible. Accurate measurements of status are important for national statistics to plan for the proper utilisation of government resources and they are especially important to evaluate the effectiveness of nutritional interventions. Many acute phase proteins (APP) are synthesised during inflammation and they are used to monitor the progress of disease and recovery but, individually, none of their lifecycles compare well with those of the nutritional biomarkers. Nevertheless, recognising the presence of inflammation can help interpret data and, using two APP, this review paper will illustrate the methods we have developed to assist interpretation of plasma retinol, ferritin and zinc concentrations in apparently healthy, HIV+, Kenyan adults.

The aim of the present paper is to give a brief overview on the role of dietary fat in carcinogenesis and as possible anticancer agents. Dietary fat is an essential nutrient and important source for the essential fatty acids (FA), linoleic and α-linolenic acids, which contribute to proper growth and development. However, dietary fat has been associated with the development of colorectal, breast, prostate, endometrial and ovarian cancers, with the type and quality of fat playing an underlying role. Tumour growth is the disruption of the homoeostatic balance regulating cell differentiation, proliferation and apoptosis and is associated with altered lipid metabolism. Animal cancer models and human cancer biopsy tissue demonstrate that a characteristic lipid profile is associated with the growth and development of neoplastic lesions. This entails alterations in membrane cholesterol, phospholipid and PUFA metabolism. Particularly, alterations in cell membrane FA metabolism involving the n-6 and n-3 PUFA, are associated with changes in membrane structure, function, cellular oxidative status, activity of enzymes and signalling pathways. These events are a driving force in sustaining the altered growth of cancerous lesions and provide unique targets for intervention/cancer modulation. Challenges in utilising FA in cancer modulation exist regarding intake and effect on cell structure and biochemical interactions within the cell in the prevention of cancer development. Therefore, utilising dietary PUFA in a specific n-6:n-3 ratio may be an important chemopreventive tool in altering the growth characteristics of cancer cells.

This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

Inflammatory bowel disease (IBD) is increasing in incidence in both the developed and the developing world. Genetic, immunological and environmental factors are known to be involved. Genome-wide studies have examined the contribution played by host genetics in the development of IBD and have estimated that genetic factors are responsible for about 25 % of the disease risk. Having an IBD-associated genotype does not always lead to development of the disease phenotype, and hence it seems likely that environmental factors are key to triggering development of the disease in genetically susceptible individuals. The gut microbiota contains more cells than its human host, and mounting evidence attests to the importance of the microbiota in the development of several diseases, including IBD, metabolic syndrome and CVD. The present paper reviews the interplay between the microbiota and the mucosal immune system in health and in IBD; and discusses the evidence base for the use of therapeutic modulation of the microbiota to prevent and treat IBD.

Carbohydrate-rich foods are an essential component of the diet, providing the glucose that is continuously required by the nervous system and some other cells and tissues in the body for normal function. There is some concern that too much carbohydrate or certain types of carbohydrate such as fructose or the high glycaemic index carbohydrate foods that produce large, rapid increases in blood glucose may be detrimental to health. This review considers these issues and also summarises the public health advice currently available in Europe and the USA concerning dietary carbohydrates. The UK Scientific Advisory Committee on Nutrition is currently reviewing carbohydrates and health, and the subsequent report should help clarify some of the concerns regarding carbohydrates and health.

Eating more seasonal food is one proposal for moving towards more sustainable consumption patterns, based on the assumption that it could reduce the environmental impact of the diet. The aim of the present paper is to consider the implications of eating seasonal food on the different elements of sustainability (i.e. health, economics, society), not just the environment. Seasonality can be defined as either globally seasonal (i.e. produced in the natural production season but consumed anywhere in the world) or locally seasonal (i.e. produced in the natural production season and consumed within the same climatic zone). The environmental, health, economic and societal impact varies by the definition used. Global seasonality has the nutritional benefit of providing a more varied and consistent supply of fresh produce year round, but this increases demand for foods that in turn can have a high environmental cost in the country of production (e.g. water stress, land use change with loss of biodiversity). Greenhouse gas emissions of globally seasonal food are not necessarily higher than food produced locally as it depends more on the production system used than transportation. Eating more seasonal food, however, is only one element of a sustainable diet and should not overshadow some of the potentially more difficult dietary behaviours to change that could have greater environmental and health benefits (e.g. reducing overconsumption or meat consumption). For future guidelines for sustainable diets to be realistic they will need to take into account modern lifestyles, cultural and social expectations in the current food environment.

The human gut microbiota has been identified as a possible novel CVD risk factor. This review aims to summarise recent insights connecting human gut microbiome activities with CVD and how such activities may be modulated by diet. Aberrant gut microbiota profiles have been associated with obesity, type 1 and type 2 diabetes and non-alcoholic fatty liver disease. Transfer of microbiota from obese animals induces metabolic disease and obesity in germ-free animals. Conversely, transfer of pathogen-free microbiota from lean healthy human donors to patients with metabolic disease can increase insulin sensitivity. Not only are aberrant microbiota profiles associated with metabolic disease, but the flux of metabolites derived from gut microbial metabolism of choline, phosphatidylcholine and l-carnitine has been shown to contribute directly to CVD pathology, providing one explanation for increased disease risk of eating too much red meat. Diet, especially high intake of fermentable fibres and plant polyphenols, appears to regulate microbial activities within the gut, supporting regulatory guidelines encouraging increased consumption of whole-plant foods (fruit, vegetables and whole-grain cereals), and providing the scientific rationale for the design of efficacious prebiotics. Similarly, recent human studies with carefully selected probiotic strains show that ingestion of viable microorganisms with the ability to hydrolyse bile salts can lower blood cholesterol, a recognised risk factor in CVD. Taken together such observations raise the intriguing possibility that gut microbiome modulation by whole-plant foods, probiotics and prebiotics may be at the base of healthy eating pyramids advised by regulatory agencies across the globe. In conclusion, dietary strategies which modulate the gut microbiota or their metabolic activities are emerging as efficacious tools for reducing CVD risk and indicate that indeed, the way to a healthy heart may be through a healthy gut microbiota.

Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1–Akt–FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid–base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required.

Health benefits or advocated health benefits of long-chain (LC) n-3 PUFA are better known by medical doctors as well as by consumers, so that consumption increases. In addition, the development of aquaculture requires more fishmeal and fish oil. Humanisation of care of companion animals is also associated with addition of LC n-3 PUFA in pet foods. The risk of the increased demand for LC n-3 PUFA is the excess harvesting of natural sources, especially of marine origin (oily fishes, krill). In order to improve sustainability, alternative sources of LC n-3 PUFA have been developed. These alternative sources are: (a) terrestrial plants naturally or genetically enriched in stearidonic acid (SDA), which bypasses the first limiting step of (i.e. ∆6 desaturase) of the biosynthesis of LC n-3 PUFA; (b) single-cell oils rich in LC n-3 PUFA (microalgae, Escherichia coli) and krill. Currently, plants rich in SDA are expensive, metabolic engineering is unfavourably accepted by consumers in many countries, cultivation of microalgae is very expensive even though their ability (for some of them) to synthesise biofuels could induce a decrease in industrial costs, and Antarctic krill harvest must be restricted. Thus, it is difficult to predict their real development in the future.

In the first years after birth, the intestinal microbiota develops rapidly both in diversity and complexity while being relatively stable in healthy adults. Different life-style-related factors as well as medical practices have an influence on the early-life intestinal colonisation. We address the impact of some of these factors on the consecutive microbiota development and later health. An overview is presented of the microbial colonisation steps and the role of the host in that process. Moreover, new early biomarkers are discussed with examples that include the association of microbiota and atopic diseases, the correlation of colic and early development and the impact of the use of antibiotics in early life. Our understanding of the development and function of the intestinal microbiota is constantly improving but the long-term influence of early-life microbiota on later life health deserves careful clinical studies.