Cereal fibre and whole-grain intakes have been consistently associated in the epidemiological literature with reduced mortality and risk of chronic disease including obesity, CVD and type 2 diabetes. The present review focuses on intervention trials with three primary aims: (1) understanding the mechanisms through which fibre consumption improves health (for example, examination of intermediate endpoints reflecting improved lipid, glucose and energy metabolism); (2) close evaluation of qualitative factors which modify fibre's effectiveness including physiochemical properties (for example, solubility, fermentability and viscosity), fibre extract molecular weight, fibre particle size and botanical structure of the fibre source grain; and (3) identification of areas in which additional research is needed. The first two aims typify the goals of nutrition research, in that improved understanding of the specific factors which determine fibre's health benefits has critical implications for dietary recommendations as well as improving understanding of physiological mechanisms. The third aim acknowledges the substantial gap between recommended and actual fibre intakes in many developed countries including the USA and the UK. In recognition of this deficit in total fibre intake, food manufacturing processes increasingly utilise fibre extracts and concentrates as food additives. However, whether fibre extracts provide similar health benefits to the fibre supplied in the constituents of whole grain is largely unexplored. The relative benefits of fibre extracts compared with whole-grain fibre sources therefore represent a critical area in which additional research is needed.

Evidence shows that both biological and nonbiological factors contribute to health disparities. Genetics, in particular, plays a part in how common diseases manifest themselves. Today, unprecedente...

Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10^-16 for CHO intake; β = −36.4 ± 5.95, P = 9.96 x 10^-10 for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10^-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A. Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)—NCT01023750; and the Framingham Heart Study (FHS)—NCT00005121.