Mammals have an endogenous timing system in the suprachiasmatic nuclei (SCN) of the hypothalamic region of the brain. This internal clock system is composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24 h (hence the term ‘circadian’). These circadian oscillations bring about rhythmic changes in downstream molecular pathways and physiological processes such as those involved in nutrition and metabolism. It is now emerging that the molecular components of the clock system are also found within the cells of peripheral tissues, including the gastrointestinal tract, liver and pancreas. The present review examines their role in regulating nutritional and metabolic processes. In turn, metabolic status and feeding cycles are able to feed back onto the circadian clock in the SCN and in peripheral tissues. This feedback mechanism maintains the integrity and temporal coordination between various components of the circadian clock system. Thus, alterations in environmental cues could disrupt normal clock function, which may have profound effects on the health and well-being of an individual.

The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P = 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P = 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P = 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P = 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.

Results from observational studies on the association of fish and n-3 fatty acid consumption with type 2 diabetes mellitus (T2DM) risk are conflicting. Hence, a meta-analysis was performed to investigate this association from cohort studies. A comprehensive search was then conducted to identify cohort studies on the association of fish and/or n-3 fatty acid intake with T2DM risk. In the highest v. lowest categorical analyses, the fixed or random-effect model was selected based on the homogeneity test among studies. Linear and non-linear dose–response relationships were also assessed by univariate and bivariate random-effect meta-regression with restricted maximum likelihood estimation. In the highest v. lowest categorical analyses, the pooled relative risk (RR) of T2DM for intake of fish and n-3 fatty acid was 1·146 (95 % CI 0·975, 1·346) and 1·076 (95 % CI 0·955, 1·213), respectively. In the linear dose–response relationship, the pooled RR for an increment of one time (about 105 g)/week of fish intake (four times/month) and of 0·1 g/d of n-3 fatty acid intake was 1·042 (95 % CI 1·026, 1·058) and 1·057 (95 % CI 1·042, 1·073), respectively. The significant non-linear dose–response associations of fish and n-3 fatty acid intake with T2DM risk were not observed. The present evidence from observational studies suggests that the intake of both fish and n-3 fatty acids might be weakly positively associated with the T2DM risk. Further studies are needed to confirm these results.

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

Angiogenesis is important for tumour vascularisation and growth, and is therefore a promising target for cancer therapy. The present study reports inhibition of in vitro angiogenesis in human umbilical vein endothelial cells (HUVEC) as well as in rat aortic rings at physiological concentrations of lycopene, that is, 1–2 μmol/l. At a final concentration of 1·15 μmol/l, a significant reduction (P < 0·05) in network branching, that is, junction numbers, the number of tubules and tubule length, was observed in both HUVEC as well as in the rat aortic rings. The inhibitory effect of lycopene was independent of the presence of the pro-angiogenic agents, vascular endothelial growth factor and TNF-α. The anti-angiogenic effects of lycopene in the present study were shown at a concentration that should be achievable by dietary means. These results extend our knowledge of one of the putative anti-cancer actions of lycopene.

We investigated the effects of prolonged treatment of diabetic rats with curcumin-supplemented yoghurt on the physiological and biochemical changes associated with diabetes mellitus. An established metabolic cage model was used to assess these changes in three groups of streptozotocin-diabetic rats which had been administered, by gavage, curcumin blended into yoghurt in the doses of 30, 60 and 90 mg/kg body weight (BW) per d (groups DC30, DC60, DC90) for 31 d. One group of non-diabetic rats was also treated with 90 mg/kg BW per d curcumin (NDC90). Three control groups of diabetic animals received water (DW), yoghurt (DY) and insulin at 27·78 μmol/d by subcutaneous injection (DI). Also, two groups of non-diabetic animals received water (NDW) and yoghurt (NDY). Groups DI and DC90 exhibited significant falls, relative to DW and DY, in food and water intake, urine volume, glycaemia, urinary urea and glucose, proteinuria, serum TAG and activities of aspartate and alanine aminotransferases, and higher hepatic glycogen and BW. These improvements were greater in DI than in DC90. No difference was observed in the serum levels of total cholesterol or HDL-cholesterol, or in the masses of adipose and muscular tissues, between DC90 and DW or DY. Moreover, the improvements in curcumin-treated rats, relative to DW and DY, were significant and dose-dependent. The NDC90 group also showed no difference from the NDW or NDY groups, in any of the markers for diabetes. In conclusion, curcumin mixed into yoghurt at the highest dose tested exhibited anti-diabetic activity, improving significantly most of the markers assessed in this study.

Little is known about the association of circulating 25-hydroxyvitamin D (25(OH)D) and blood pressure (BP) parameters, including systolic and diastolic BP, pulse pressure (PP), mean arterial pressure (MAP) and hypertension in non-Western populations that have not yet been exposed to foods fortified with vitamins and seldom use vitamin D supplements. A cross-sectional analysis of plasma 25(OH)D levels in association with BP measures was performed for 1460 participants (1055 women and 405 men, aged 40–74 years) of two large cohort studies in Shanghai. Multivariable linear and logistic regressions were conducted. Overall, the prevalence of vitamin D deficiency was 55·8 % using National Health and Nutrition Examination Survey, USA criteria and 29·9 % using WHO criteria. The median plasma 25(OH)D level in the population was 38·0 nmol/l for men and 33·6 nmol/l for women (P < 0·01) among participants who were not on antihypertensive drugs. Among men, BP parameters (systolic BP, diastolic BP and MAP) were significantly and inversely associated with higher quintiles of 25(OH)D compared with the lowest quintile (Ptrend < 0·05 for all). Vitamin D non-deficient status (WHO criteria) was inversely associated with hypertension (ORadjusted = 0·29; 95 % CI 0·10, 0·82). An inverse association was also found between hypertension and the highest quintile of 25(OH)D (ORadjusted = 0·16; 95 % CI 0·04, 0·65 for ≥ 50·6 nmol/l; Ptrend = 0·02). Among women, no significant associations were found for BP parameters and hypertension. The present study shows that vitamin D deficiency is common among adults in urban China. Circulating 25(OH)D levels were inversely related to the levels of individual BP parameters and hypertension among middle-aged and elderly men but not among women. More research is needed to investigate the potential sex differential associations.

There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) model in vitro. Live cells of lactobacilli (Lactobacillus casei Shirota, L. rhamnosus GG, L. plantarum NCIMB 8826 and L. reuteri NCIMB 11951) and bifidobacteria (Bifidobacterium longum SP 07/3 and B. bifidum MF 20/5) were individually incubated with PBMC from seven healthy subjects for 24 h. Probiotic strains increased the proportion of CD69+ on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1β, IL-6, IL-10, TNF-α, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1α to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-β. The cytokines that showed strain-specific modulation included IL-10, interferon-γ, TNF-α, IL-12p70, IL-6 and monocyte chemotactic protein-1. The Lactobacillus strains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti-inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains.

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic microbial composition, immune parameters, bowel habits and quality of life were investigated. PDX is a complex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus–Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different. PDX was shown to be slowly degraded in the colon, and the fermentation significantly reduced the genotoxicity of the faecal water. PDX also affected bowel habits of the subjects, as less abdominal discomfort was recorded and there was a trend for less hard and more formed stools during PDX consumption. Furthermore, reduced snacking was observed upon PDX consumption. This study demonstrated the impact of PDX on the colonic microbiota and showed some potential for reducing the risk factors that may be associated with colon cancer initiation.

The effects of the anti-methanogenic compound, bromochloromethane (BCM), on rumen microbial fermentation and ecology were examined in vivo. Japanese goats were fed a diet of 50 % Timothy grass and 50 % concentrate and then sequentially adapted to low, mid and high doses of BCM. The goats were placed into the respiration chambers for analysis of rumen microbial function and methane and H2 production. The levels of methane production were reduced by 5, 71 and 91 %, and H2 production was estimated at 545, 2941 and 3496 mmol/head per d, in response to low, mid and high doses of BCM, respectively, with no effect on maintenance feed intake and digestibility. Real-time PCR quantification of microbial groups showed a significant decrease relative to controls in abundance of methanogens and rumen fungi, whereas there were increases in Prevotella spp. and Fibrobacter succinogenes, a decrease in Ruminococcus albus and R. flavefaciens was unchanged. The numbers of protozoa were also unaffected. Denaturing gradient gel electrophoresis and quantitative PCR analysis revealed that several Prevotella spp. were the bacteria that increased most in response to BCM treatment. It is concluded that the methane-inhibited rumen adapts to high hydrogen levels by shifting fermentation to propionate via Prevotella spp., but the majority of metabolic hydrogen is expelled as H2 gas.

Long-chain n-3 PUFA can lower blood pressure (BP) but their acute effects on cardiac output, BP and systemic vascular resistance (SVR) in response to dynamic exercise are uncertain. We compared the effects of high-fat meals rich in EPA (20 : 5n-3), DHA (22 : 6n-3) or oleic acid (control) on cardiac output, BP and SVR in response to exercise stress testing. High-fat meals (50 g fat) containing high-oleic sunflower oil enriched with 4·7 g of either EPA or DHA v. control (high-oleic sunflower oil only) were fed to twenty-two healthy males using a randomised cross-over design. Resting measurements of cardiac output, heart rate and BP were made before and hourly over 5 h following the meal. A standardised 12 min exercise test was then conducted with further measurements made during and post-exercise. Blood samples were collected at fasting, 5 h postprandially and immediately post-exercise for the analysis of lipid, glucose and 8-isoprostane-F2α (8-iso-PGF2α). Plasma concentrations of EPA and DHA increased by 0·22 mmol/l 5 h following the EPA and DHA meals, respectively, compared with the control (P < 0·001). Resting cardiac output and 8-iso-PGF2α increased similarly following all meals and there were no significant differences in cardiac output during exercise between the meals. SVR was lower at 5 h and during exercise following the DHA but not EPA meal, compared with the control meal, by 4·9 % (95 % CI 1·3, 8·4; P < 0·01). Meals containing DHA appear to differ from EPA with regard to their effects on cardiovascular haemodynamics during exercise.

Ageing is an important determinant of atherosclerosis development rate, mainly by the creation of a chronic low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in the fasting and postprandial states. Our aim was to study the effects of dietary fat on the expression of genes related to inflammation (NF-κB, monocyte chemoattractant protein 1 (MCP-1), TNF-α and IL-6) and plaque stability (matrix metalloproteinase 9, MMP-9) during the postprandial state of twenty healthy, elderly people who followed three diets for 3 weeks each: (1) Mediterranean diet (Med Diet) enriched in MUFA with virgin olive oil; (2) SFA-rich diet; and (3) low-fat, high-carbohydrate diet enriched in n-3 PUFA (CHO-PUFA diet) by a randomised crossover design. At the end of each period, after a 12-h fast, the subjects received a breakfast with a composition similar to the one when the dietary period ended. In the fasting state, the Med Diet consumption induced a lower gene expression of the p65 subunit of NF-κB compared with the SFA-rich diet (P = 0·019). The ingestion of the Med Diet induced a lower gene postprandial expression of p65 (P = 0·033), MCP-1 (P = 0·0229) and MMP-9 (P = 0·041) compared with the SFA-rich diet, and a lower gene postprandial expression of p65 (P = 0·027) and TNF-α (P = 0·047) compared with the CHO-PUFA diet. Direct plasma quantification mostly reproduced the findings. Our data suggest that consumption of a Med Diet reduces the postprandial inflammatory response in mononuclear cells compared with the SFA-rich and CHO-PUFA diets in elderly people. These findings may be partly responsible for the lower CVD risk found in populations with a high adherence to the Med Diet.

Pulses are low glycaemic foods; however, their effect on satiation is unknown. The objective was to determine the effects of an ad libitum pulse meal on food intake (FI), appetite and blood glucose (BG) before and after a test meal (4 h later) and on FI at the test meal. Males (n 24, 22·8 kg/m2) received one of four treatments or control. The pulse treatments contained pasta and tomato sauce and 44 % of energy from: (1) chickpeas, (2) lentils, (3) navy beans or (4) yellow peas. The control was pasta and tomato sauce (pasta and sauce). FI (satiation) was measured at the treatment meal (0–20 min) and at an ad libitum pizza meal 4 h later. BG and appetite were measured from 0 to 340 min. At the treatment meal, lentils led to lower FI compared to chickpeas and pasta and sauce, whereas navy beans led to lower FI compared to chickpeas. Also, lentils led to lower cumulative FI compared to pasta and sauce. All pulses led to lower BG peak and cumulative area under the curve (AUC; 0–340 min); however, only chickpeas, lentils and navy beans reduced pre-pizza meal BG AUC (0–260 min) relative to pasta and sauce. Chickpeas led to lower post-pizza meal BG AUC (260–340 min) compared to navy beans and yellow peas. Consumption of pulses in a high-glycaemic meal contributes to earlier satiation, lower BG following the meal and after a later meal, but these effects are specific to pulse type and cannot be explained by their glycaemic properties alone.

The objectives of the present study were to identify dietary patterns independently in first-time mothers and fathers, and to examine whether these patterns were correlated within families. Dietary intakes were collected at baseline in the Melbourne Infant Feeding Activity and Nutrition Trial Program using a validated FFQ in 454 pairs of first-time mothers and fathers. Education level was reported in associated questionnaires. Principal components analyses included frequencies of fifty-five food groups and were performed independently in mothers and fathers. Spearman's correlation coefficients were used to assess associations between dietary pattern scores. A total of four dietary patterns were identified in mothers and fathers. Of these, three dietary patterns had similar characteristics between these two populations, namely ‘Fruits and vegetables’, ‘High-energy snack and processed foods’, ‘High-fat foods’ in mothers; and ‘Fruits’, ‘High-energy snack and processed foods’, ‘High-fat foods’ in fathers. The following two additional patterns were identified: ‘Cereals and sweet foods’ in mothers and ‘Potatoes and vegetables’ in fathers. Patterns incorporating healthier food items were found to be positively associated with parent education. An inverse association with education was found for the ‘High-fat foods’ and ‘High-energy snack and processed foods’ dietary patterns. Qualitatively similar patterns between corresponding mothers and fathers were the most strongly correlated (ρ = 0·34–0·45, P < 0·001). There were some differences in dietary patterns between mothers and fathers, suggesting that it is worth deriving patterns separately when considering couples, and more generally between men and women. Exploring how these various patterns correlate within households provides important insights to guide the development and implementation of family-based interventions.

The aim of the present study was to calculate the distribution of total iodine intake among Flemish preschoolers and to identify the major sources contributing to iodine intake. A simulation model using a combination of deterministic and probabilistic techniques was utilised. Scenario analyses were performed to assess iodine intake via dairy products, industrially added iodised salt in bread and discretionarily added iodised household salt. Relevant data from 3-d estimated dietary records of 696 preschoolers 2·5–6·5 years old were used. Usual iodine intakes were calculated using the Iowa State University method. With a more generalised utilisation of iodised salt in bread (44 % of the bakers in 2011 instead of 12 % in 2002), mean iodine intake increased from 159 to 164 μg/d using the McCance and Widdowson's food composition table and from 104 to 109 μg/d using the German food composition table. The percentage of preschoolers with an iodine intake below the estimated average requirement (65 μg/d) decreased from 5–12 to 4–9 %, while the percentage of preschoolers with an iodine intake above the tolerable upper intake level (300 μg/d) remained constant (0·3–4 %). Mean iodine intake via food supplements was 4·2 μg/d (total population) and 16·9 μg/d (consumers only). Both in 2002 and 2011, sugared dairy products, milk and iodised salt (21·4, 13·1, and 8·7 %, respectively in 2011) were the main contributors to total iodine intake. In conclusion, dietary iodine intake could still be improved in Flemish preschoolers. The use of adequately iodised household salt and the more generalised use of iodised salt by bakers should be further encouraged.

Many dietary recommendations include reduction of excessive intake of sugar-sweetened beverages (SSB) and other energy-rich beverages such as juices and alcohol. The present study examines surveys of both individual dietary intake data and household food expenditure surveys to provide a picture of patterns and trends in beverage intake and purchases in Great Britain from 1986 to 2009, and estimates the potential for pricing policy to promote more healthful beverage purchase patterns. In 2008–9, beverages accounted for 21, 14 and 18 % of daily energy intake for children aged 1·5–18 and 4–18 years, and adults (19–64 years), respectively. Since the 1990s, the most important shifts have been a reduction in consumption of high-fat dairy products and an increased consumption of fruit juices and reduced-fat milk among preschoolers, children and adolescents. Among adults, consumption of high-fat milk beverages, sweetened tea and coffee and other energy-containing drinks fell, but reduced-fat milk, alcohol (particularly beer) and fruit juice rose. In testing taxation as an option for shifting beverage purchase patterns, we calculate that a 10 % increase in the price of SSB could potentially result in a decrease of 7·5 ml/capita per d. A similar 10 % tax on high-fat milk is associated with a reduction of high-fat milk purchases by 5 ml/capita per d and increased reduced-fat milk purchase by 7 ml/capita per d. This analysis implies that taxation or other methods of shifting relative costs of these beverages could be a way to improve beverage choices in Great Britain.