Dietary strategies that can help reduce hunger and promote fullness are beneficial for weight control, since these are major limiting factors for success. High-protein (HP) diets, specifically those that maintain the absolute number of grams ingested, while reducing energy, are a popular strategy for weight loss (WL) due to the effects of protein-induced satiety to control hunger. Nonetheless, both the safety and efficacy of HP WL diets have been questioned, particularly in combination with low-carbohydrate advice. Nonetheless, for short-to-medium-term intervention studies (over several months), increasing the energetic contribution of protein does appear effective. The effects of HP diets on appetite, bone health, renal function, blood pressure, cardiovascular bio-markers, antioxidant status, gut health and psychological function are discussed. Further research is warranted to validate the physiological effects of HP diets over longer periods of time, including studies that modify the quality of macronutrients (i.e. the type of carbohydrate, fat and protein) and the interaction with other interventions (e.g. exercise and dietary supplements).

Molecular mechanisms underlying brain structure and function are affected by nutrition throughout the life cycle, with profound implications for health and disease. Responses to nutrition are in turn influenced by individual differences in multiple target genes. Recent advances in genomics and epigenomics are increasing understanding of mechanisms by which nutrition and genes interact. This review starts with a short account of current knowledge on nutrition–gene interactions, focusing on the significance of epigenetics to nutritional regulation of gene expression, and the roles of SNP and copy number variants (CNV) in determining individual responses to nutrition. A critical assessment is then provided of recent advances in nutrition–gene interactions, and especially energy status, in three related areas: (i) mental health and well-being, (ii) mental disorders and schizophrenia, (iii) neurological (neurodevelopmental and neurodegenerative) disorders and Alzheimer's disease. Optimal energy status, including physical activity, has a positive role in mental health. By contrast, sub-optimal energy status, including undernutrition and overnutrition, is implicated in many disorders of mental health and neurology. These actions are mediated by changes in energy metabolism and multiple signalling molecules, e.g. brain-derived neurotrophic factor (BDNF). They often involve epigenetic mechanisms, including DNA methylation and histone modifications. Recent advances show that many brain disorders result from a sophisticated network of interactions between numerous environmental and genetic factors. Personal, social and economic costs of sub-optimal brain health are immense. Future advances in understanding the complex interactions between nutrition, genes and the brain should help to reduce these costs and enhance quality of life.

In Europe, for authorisation of a health claim, applicants must follow the procedures in the legislation and in the guidelines for submission of a dossier set out by the European Food Safety Authority. The Functional Foods in Europe (FUFOSE) and Process for the Assessment of Scientific Support for Claims on Foods (PASSCLAIM) projects underpinned the laws and provided criteria against which the quality of the totality of the available data could be judged. Whereas the regulations and PASSCLAIM require an assessment of the extent to which cause and effect can be demonstrated between a food category, a food or constituent and a health benefit, the European Food Safety Authority requires conclusive evidence of cause and effect. This latter standard of proof and a focus on randomised controlled trials done on isolated components and using validated physiological biomarkers may not always be appropriate to assess nutrition science. The aims of this paper are to address the strengths and weaknesses of different sources of evidence that contribute to the totality of the available data, to undertake a critical examination of the application of a drug-like assessment model in evidence-based nutrition and to encourage research on new biomarkers of health and homeostatic adaptability. There is a need for (a) a robust and pragmatic scientific framework for assessing the strength, consistency and biological plausibility of the evidence, and (b) consumer understanding research on claims that use qualifying language and/or graphics to reflect the weight of evidence. Such scientific, policy and communication approaches are proportionate and could help stimulate academic research, promote fair trade and product innovation and contribute to consumer education about food and health.

Unsaturated fatty acids are ligands of PPAR-γ, which up-regulates genes involved in fatty acid transport and TAG synthesis and the insulin-sensitising adipokine adiponectin, which activates fatty acid β-oxidation via PPAR-α action in liver. We investigated the effect of dietary fatty acid interaction with PPARG, PPARA and ADIPOQ gene variants on plasma lipid and adiponectin concentrations in the Reading Imperial Surrey Cambridge King's study, a five-centre, parallel design, randomised controlled trial of 466 subjects at increased cardiometabolic risk. After a 4-week run-in to baseline, SFA was replaced by MUFA or carbohydrate (low fat) in isoenergetic diets for 24 weeks. Habitual dietary PUFA:SFA ratio×PPARG Pro12Ala genotype interaction influenced plasma total cholesterol (P=0·02), LDL-cholesterol (P=0·002) and TAG (P=0·02) concentrations in White subjects. PPARA Val162Leu×PPARG Pro12Ala genotype interaction influenced total cholesterol (P=0·04) and TAG (P=0·03) concentrations at baseline. After high-MUFA and low-fat diets, total cholesterol and LDL-cholesterol were reduced (P<0·001) and gene×gene interaction determined LDL-cholesterol (P=0·003) and small dense LDL as a proportion of LDL (P=0·012). At baseline, ADIPOQ −10066 G/A A-allele was associated with lower serum adiponectin (n 360; P=0·03) in White subjects. After the high-MUFA diet, serum adiponectin increased in GG subjects and decreased in A-allele carriers (P=0·006 for difference). In GG, adiponectin increased with age after the high MUFA and decreased after the low-fat diet (P=0·003 for difference at 60 years). In conclusion, in Whites, high dietary PUFA:SFA would help to reduce plasma cholesterol and TAG in PPARG Ala12 carriers. In ADIPOQ −10066 GG homozygotes, a high-MUFA diet may help to increase adiponectin with advancing age.

The current review considers satiety-based approaches to weight management in the context of health claims. Health benefits, defined as beneficial physiological effects, are what the European Food Safety Authority bases their recommendations on for claim approval. The literature demonstrates that foods that target within-meal satiation and post-meal satiety provide a plausible approach to weight management. However, few ingredient types tested produce the sustainable and enduring effects on appetite accompanied by the necessary reductions in energy intake required to claim satiety/reduction in hunger as a health benefit. Proteins, fibre types, novel oils and carbohydrates resistant to digestion all have the potential to produce beneficial short-term changes in appetite (proof-of-concept). The challenge remains to demonstrate their enduring effects on appetite and energy intake, as well as the health and consumer benefits such effects provide in terms of optimising successful weight management. Currently, the benefits of satiety-enhancing ingredients to both consumers and their health are under researched. It is possible that such ingredients help consumers gain control over their eating behaviour and may also help reduce the negative psychological impact of dieting and the physiological consequences of energy restriction that ultimately undermine weight management. In conclusion, industry needs to demonstrate that a satiety-based approach to weight management, based on single-manipulated food items, is sufficient to help consumers resist the situational and personal factors that drive overconsumption. Nonetheless, we possess the methodological tools, which when employed in appropriate designs, are sufficient to support health claims.

Diet is a major factor in the aetiology of colorectal cancer (CRC). Epidemiological evidence suggests that folate confers a modest protection against CRC risk. However, the relationship is complex, and evidence from human intervention trials and animal studies suggests that a high-dose of folic acid supplementation may enhance the risk of colorectal carcinogenesis in certain circumstances. The molecular mechanisms underlying the apparent dual modulatory effect of folate on colorectal carcinogenesis are not fully understood. Folate is central to C1metabolism and is needed for both DNA synthesis and DNA methylation, providing plausible biological mechanisms through which folate could modulate cancer risk. Aberrant DNA methylation is an early event in colorectal carcinogenesis and is typically associated with the transcriptional silencing of tumour suppressor genes. Folate is required for the production of S-adenosyl methionine, which serves as a methyl donor for DNA methylation events; thereby folate availability is proposed to modulate DNA methylation status. The evidence for an effect of folate on DNA methylation in the human colon is limited, but a modulation of DNA methylation in response to folate has been demonstrated. More research is required to clarify the optimum intake of folate for CRC prevention and to elucidate the effect of folate availability on DNA methylation and the associated impact on CRC biology.

Over the last three decades, dietary pattern analysis has come to the forefront of nutritional epidemiology, where the combined effects of total diet on health can be examined. Two analytical approaches are commonly used: a priori and a posteriori. Cluster analysis is a commonly used a posteriori approach, where dietary patterns are derived based on differences in mean dietary intake separating individuals into mutually exclusive, non-overlapping groups. This review examines the literature on dietary patterns derived by cluster analysis in adult population groups, focusing, in particular, on methodological considerations, reproducibility, validity and the effect of energy mis-reporting. There is a wealth of research suggesting that the human diet can be described in terms of a limited number of eating patterns in healthy population groups using cluster analysis, where studies have accounted for differences in sex, age, socio-economic status, geographical area and weight status. Furthermore, patterns have been used to explore relationships with health and chronic diseases and more recently with nutritional biomarkers, suggesting that these patterns are biologically meaningful. Overall, it is apparent that consistent trends emerge when using cluster analysis to derive dietary patterns; however, future studies should focus on the inconsistencies in methodology and the effect of energy mis-reporting.

Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus.