Due to their ubiquitous distribution, flavonoids from different classes are commonly present together in foods. However, little is known about the interactions between them. The flavonol quercetin and the flavan-3-ol (+)-catechin are among the most abundant flavonoids in the diet. In the present study, we have analysed the interactions between these two flavonoids on vascular function using two pure compounds and mixtures of these flavonoids in 1:0·1, 1:1 or 1:10 proportions. Quercetin induced a more potent concentration-dependent relaxant effect than catechin in the isolated rat aorta, and the isobolographic analysis of the mixtures showed no synergistic or antagonistic effects between them, i.e. their effects were additive. Quercetin was more potent in mesenteric than in pulmonary arteries. Catechin had weak effects in these vessels and did not modify the effects of quercetin. Endothelial dysfunction induced by increased oxidative stress by the superoxide dismutase inhibitor diethyldithiocarbamate was prevented by quercetin, whereas catechin showed a weak effect and the 1:1 mixture an intermediate effect compared with the pure compounds. Quercetin but not catechin showed a pro-oxidant and NO-scavenging effect, which was not prevented by catechin. In conclusion, catechin was less potent than quercetin as a vasodilator, pro-oxidant or to prevent endothelial dysfunction, and there were no synergistic interactions between quercetin and catechin.

Accumulating evidence suggests that changes in dietary folate intake may modulate the risks of Alzheimer's disease (AD) through as yet unknown mechanisms. The aims of the present study were to investigate how dietary folate affects the brain folate distribution, levels of oxidised lipid and DNA damage in the absence/presence of β-amyloid(25–35) (Aβ) peptide challenge, a pathogenic hallmark of AD. Male Wistar rats were assigned to diets with folic acid at 0 (folate deprivation; FD), 8 (moderate folate; MF) and 8 mg folic acid/kg diet+0·003 % in drinking-water (folate supplementation; FS) for 4 weeks. A single injection of Aβ peptide (1 mg/ml) or the vehicle solution was intracerebroventricularly (icv) administrated to rats a week before killing. Brain folate, a marker of oxidative injury, and neuronal death were assayed. In the absence of an Aβ injection, FD rats showed reduced folate levels, and increased 2-thiobarbituric acid-reactive substances and a mitochondrial (mt)DNA 4834 bp large deletion (mtDNA4834 deletion) in the hippocampus compared with the counterpart brains of control rats (P < 0·05). A single icv injection of Aβ peptide potentiated lipid peroxidation in the medulla of FD rats, which was ameliorated by feeding FD rats with the MF and FS diets (P < 0·05). Feeding the FS diet to Aβ-injected rats enriched brain folate levels and reduced mtDNA4834 deletion in the hippocampal and medullary regions compared with corresponding tissues of Aβ+FD rats (P < 0·05). Aβ+FS rats had reduced rates of neuronal death in the frontal cortex compared with Aβ+FD rats (P < 0·05). Taken together, our data revealed that folate deprivation differentially depleted brain folate levels, and increased lipid peroxidation and mtDNA4834 deletions, particularly, in the hippocampus. Upon Aβ challenge, the FS diet may protect various brain regions against lipid peroxidation, mitochondrial genotoxicity and neural death associated with folate deprivation.

Cordyceps sinensis (CS) is a traditional Chinese medicine and health food used to support many organ systems. It is commercially produced by cultivation in a liquid medium or on a solid (grain/potato) phase. We tested the effects of hot water extracts of liquid-phase and solid-phase commercially grown CS on its ability to influence proliferation (using Alamar blue, an oxidation/reduction indicator), migration (serial-wounded monolayer photomicroscopy), invasion through collagen gel (fluorometric assay) and indomethacin-induced apoptosis (active caspase-3 colorimetric assay) of human colon cancer HT29 cells. An in vivo study used a rat gastric damage model (indomethacin 20 mg/kg and 4 h restraint with oral administration). The CS extract stimulated cell proliferation threefold when added at 10 μg/ml (P < 0·01). Cell migration increased by 69 % and invasion by 17 % when CS was added at 5 mg/ml (P < 0·01). The results also showed that 93 % of the pro-proliferative activity was soluble in ethanol, whereas pro-migratory activity was divided (61:49) into both ethanol-soluble and ethanol-insoluble sub-fractions. Indomethacin-induced apoptosis was not affected by the presence of CS. CS reduced the amount of gastric injury by 63 % when administered orally at 20 mg/ml (P < 0·01), the results being similar to using the potent cytoprotective agent epidermal growth factor at 25 μg/ml (83 % reduction). We conclude that both methods of cultivated CS possess biological activity when analysed using a variety of gut models of injury and repair. Functional foods, such as CS, could provide a novel approach for the prevention and treatment of injury to the bowel.

We previously reported that, in rodents, a diet with a high oxidised frying oil (OFO) content leads to glucose intolerance associated with a reduction in insulin secretion. The present study aimed at investigating the impairment of pancreatic islets caused by dietary OFO. C57BL/6J mice were divided into three groups to receive a low-fat basal diet containing 5 g/100 g of fresh soyabean oil (LF group) or a high-fat diet containing 20 g/100 g of either fresh soyabean oil (HF group) or OFO (HO group). After 8 weeks, mice in the HO group showed glucose intolerance and hypoinsulinaemia, and their islets showed impaired glucose-stimulated insulin secretion (P < 0·05; HO group v. LF and HF groups). Significantly higher oxidative stress and a lower mitochondrial membrane potential were observed in the islets in the HO group compared with the LF and HF groups. Immunoblots showed that the reduction in insulin levels in HO islets was associated with activation of the c-Jun NH2-terminal kinase and a reduction in levels of pancreatic and duodenal homeobox factor-1. In a second study, when dietary OFO-induced tissue vitamin E depletion was prevented by large-dose vitamin E supplementation (500 IU(1·06 mmol all-rac-α-tocopherol acetate)/kg diet; HO+E group), the OFO-mediated reduction in islet size and impairment of glucose tolerance and insulin secretion were significantly attenuated (P < 0·05; HO group v. HO+E group). We conclude that a high level of dietary OFO ingestion impairs glucose metabolism by causing oxidative damage and compromising insulin secretion in pancreatic islets, and that these effects can be prevented by vitamin E supplementation.

In vitro, both carbohydrate sugars and artificial sweeteners (AS) stimulate the secretion of glucagon-like peptide-1 (GLP-1). It has been suggested that the gut tastes sugars and AS through the same mechanisms as the tongue, with potential effects on gut hormone release. We investigated whether the human gut responds in the same way to AS and carbohydrate sugars, which are perceived by lingual taste as equisweet. We focused on the secretion of gastrointestinal (GI) satiety peptides in relation to appetite perception. We performed a placebo-controlled, double-blind, six-way, cross-over trial including twelve healthy subjects. On separate days, each subject received an intragastric infusion of glucose, fructose or an AS (aspartame, acesulfame K and sucralose) dissolved in 250 ml of water or water only (control). In a second part, four subjects received an intragastric infusion of the non-sweet, non-metabolisable sugar analogue 2-deoxy-d-glucose. Glucose stimulated GLP-1 (P = 0·002) and peptide tyrosine tyrosine (PYY; P = 0·046) secretion and reduced fasting plasma ghrelin (P = 0·046), whereas fructose was less effective. Both carbohydrate sugars increased satiety and fullness (albeit not significantly) compared with water. In contrast, equisweet loads of AS did not affect gastrointestinal peptide secretion with minimal effects on appetite. 2-Deoxy-d-glucose increased hunger ratings, however, with no effects on GLP-1, PYY or ghrelin. Our data demonstrate that the secretion of GLP-1, PYY and ghrelin depends on more than the detection of (1) sweetness or (2) the structural analogy to glucose.

The activation of PPARγ by ligands, including conjugated linoleic acid (CLA) isomers, plays an important role in the immune response. Among CLA isomers, trans-10, cis-12 (t10c12)-CLA is known to participate in the modulation of pro-inflammatory cytokine secretion. The aim of the present study was to assess the effect of t10c12-CLA on PPARγ activation, NF-κB activation and TNF-α expression in lipopolysaccharide (LPS)-naive and LPS-stimulated porcine peripheral blood mononuclear cells (PBMC). In addition, the effect of PPARγ inhibition on NF-κB activation and TNF-α expression in porcine PBMC was examined. t10c12-CLA was found to increase TNF-α expression and NF-κB activity in LPS-naive porcine PBMC. In contrast, t10c12-CLA decreased TNF-α expression and NF-κB activity in LPS-stimulated porcine PBMC. t10c12-CLA up-regulated PPARγ activity and mRNA expression in both LPS-naive and LPS-stimulated porcine PBMC. GW9662, a PPARγ antagonist, completely negated the modulating effects of t10c12-CLA on TNF-α expression and NF-κB activity in both LPS-naive and LPS-stimulated porcine PBMC. These results suggest that t10c12-CLA can modulate TNF-α production and NF-κB activation by a PPARγ-dependent pathway in porcine PBMC.

Historically, measurement of gastrointestinal transit time has required collection and X-raying of faecal samples for up to 7 d after swallowing radio-opaque markers; a tedious, labour-intensive technique for both subjects and investigators. Recently, a wireless motility capsule (SmartPill®), which uses gut pH, pressure and temperature to measure transit time, has been developed. This device, however, has not been validated with dietary interventions. Therefore, we conducted a controlled cross-over trial to determine whether the device could detect a significant difference in transit time after ten healthy subjects (five men and five women) consumed 9 g of wheat bran (WB) or an equal volume, low-fibre control for 3 d. A paired t test was used to determine differences in transit times. Colonic transit time decreased by 10·8 (sd 6·6) h (P = 0·006) on the WB treatment. Whole-gut transit time also decreased by 8·9 (sd 5·4) h (P = 0·02) after the consumption of WB. Gastric emptying time and small-bowel transit time did not differ between treatments. Despite encouraging results, the present study had several limitations including short duration, lack of randomisation and unusable data due to delayed gastric emptying of the capsule. With minimal participant burden, the SmartPill technology appears to be a potentially useful tool for assessing transit time after a dietary intervention. This technology could be considered for digestive studies with novel fibres and other ingredients that are promoted for gut health.

There is emerging evidence to show that high levels of NEFA contribute to endothelial dysfunction and impaired insulin sensitivity. However, the impact of NEFA composition remains unclear. A total of ten healthy men consumed test drinks containing 50 g of palm stearin (rich in SFA) or high-oleic sunflower oil (rich in MUFA) on separate occasions; a third day included no fat as a control. The fats were emulsified into chocolate drinks and given as a bolus (approximately 10 g fat) at baseline followed by smaller amounts (approximately 3 g fat) every 30 min throughout the 6 h study day. An intravenous heparin infusion was initiated 2 h after the bolus, which resulted in a three- to fourfold increase in circulating NEFA level from baseline. Mean arterial stiffness as measured by digital volume pulse was higher during the consumption of SFA (P < 0·001) but not MUFA (P = 0·089) compared with the control. Overall insulin and gastric inhibitory peptide response was greater during the consumption of both fats compared with the control (P < 0·001); there was a second insulin peak in response to MUFA unlike SFA. Consumption of SFA resulted in higher levels of soluble intercellular adhesion molecule-1 (sI-CAM) at 330 min than that of MUFA or control (P ≤ 0·048). There was no effect of the test drinks on glucose, total nitrite, plasminogen activator inhibitor-1 or endothelin-1 concentrations. The present study indicates a potential negative impact of elevated NEFA derived from the consumption of SFA on arterial stiffness and sI-CAM levels. More studies are needed to fully investigate the impact of NEFA composition on risk factors for CVD.

We examined the relationship between dietary folate intake and periconceptional use of folic acid (FA) supplements, and small-for-gestational age for weight (SGA-W) and height (SGA-H). The study is based on 786 Spanish women aged 16 years or above, who attended the first-term prenatal population-based screening programme (10–13 weeks) at the reference hospital ‘La Fe’, Valencia, with singleton pregnancy. Periconceptional use of FA supplements was categorised as non-users, moderate users ( ≤ 1 mg/d) and high users (>1 mg/d). Babies born to mothers who used high doses of FA supplements had a significant reduction in mean birth height compared with babies of non-users (β = − 0·53, 95 % CI − 0·96, − 0·09). As regards weight, mothers using moderate and high doses of FA supplements had lower-birth-weight babies for gestational age than non-users (β = − 22·96, 95 % CI − 101·14, 55·23; β = − 89·72, 95 % CI − 188·64, 9·21, respectively), although these decreases were not significant. Results from the multivariate logistic regression models showed that high FA supplement users had a higher significant risk for SGA-H (OR 5·33, 95 % CI 2·08, 13·7), and that users of moderate doses were not associated with a higher risk of either a SGA-W or a SGA-H baby. In contrast, increased quintiles of the dietary intake of folate were associated with a decreased risk of SGA-W (P for trend = 0·002), although no association was observed for SGA-H. Our findings suggest that periconceptional use of FA supplements greater than 1 mg/d is associated with decreased birth height and may entail a risk of decreased birth weight.

Due to the anti-inflammatory properties of PUFA, it has been suggested that they may protect against kidney damage in adults. However, relatively few epidemiological studies have examined this hypothesis in human subjects. We investigated the association between dietary intakes of PUFA (n-3, n-6 and α-linolenic acid), fish and the prevalence of chronic kidney disease (CKD). A total of 2600 Blue Mountains Eye Study (1997–9) participants aged ≥ 50 years were analysed. Dietary data were collected using a semi-quantitative FFQ, and PUFA and fish intakes were calculated. Baseline biochemistry including serum creatinine was measured. Moderate CKD was defined as an estimated glomerular filtration rate of < 60 ml/min per 1·73 m2. Participants in the highest quartile of long-chain n-3 PUFA intake had a significantly reduced likelihood of having CKD compared with those in the lowest quartile of intake (multivariable-adjusted OR 0·69, 95 % CI 0·49, 0·99). α-Linolenic acid intake was positively associated with CKD (OR, per standard deviation increase in α-linolenic acid, 1·18, 95 % CI 1·05, 1·32). Total n-3 PUFA or total n-6 PUFA were not significantly associated with CKD. The highest compared with the lowest quartile of fish consumption was associated with a reduced likelihood of CKD (OR 0·68, 95 % CI 0·48, 0·97; P for trend = 0·02). The present study shows that an increased dietary intake of long-chain n-3 PUFA and fish reduces the prevalence of CKD. Hence, a diet rich in n-3 PUFA and fish could have a role in maintaining healthy kidney function, in addition to roles of these nutrients in the prevention and modulation of other diseases.

Besides providing n-3 fatty acids with nutritional and health benefits, seafood consumption may contribute to the reduction of nutrient prevalences of inadequacy. To evaluate the contributions of seafood and other food groups to nutrient intakes of frequent seafood consumers, food consumption was evaluated through an FFQ on 991 French men and women (18–81 years) consuming seafood at least twice a week. Intakes, prevalence of inadequacies, risks of upper limit excess and food contributions to intakes were assessed for thirty-three nutrients. Mean fat contributions to total energy intakes (38·3 and 39·0 % for men and women, respectively) met French recommendations, but mean carbohydrate intakes (40·9 and 39·7 %, respectively) were insufficient. Micronutrient inadequacies were lower than in the French general population, the highest being for vitamin C (41·3 and 40·1 % for men and women, respectively), vitamin E (35·0 and 35·3 % for men and women, respectively) and Mg (37·5 and 25·5 % for men and women, respectively). Upper safety limits (USL) were exceeded mostly for Zn (6·2 %), Ca (3·7 %), retinol (2·0 %) and Cu (0·9 %). Mean contributions of seafood to vitamin D, B12, I and Se intakes ranged 40–65 %. Molluscs and crustaceans significantly contributed to vitamin B12 (13·7 %), Cu (11·4 %), Fe (11·5 %), Zn (8·4 %) and I (6·1 %) intakes, and canned fish contributed to vitamin D intake (13·4 %). Besides fish, contributions of mollusc and crustacean consumption to nutrient intakes should be considered from a public health viewpoint. Consuming seafood at least twice a week induces moderate inadequacies and risks of exceeding USL for some micronutrients, whereas macronutrient intakes remained imbalanced.

Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts. The study included 537 non-smoking women aged 50–65 years who participated in the Diet, Cancer and Health cohort (1993–97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th percentile 8, 95th percentile 49). Of the dietary factors studied, intakes of coffee and chips were statistically significantly associated with a 4 % per 200 g/d (95 % CI 2, 7; P < 0·0001) and an 18 % per 5 g/d (95 % CI 6, 31; P = 0·002) higher Hb-AA, respectively. This model explained 17 % of the variation in Hb-AA. Intakes of coffee and biscuits/crackers were statistically significantly associated with a 3 % per 200 g/d (95 % CI 1, 6; P = 0·005) and 12 % per 10 g/d (95 % CI 3, 23; P = 0·01) higher Hb-GA, respectively. This model explained 12 % of the variation in Hb-GA. In conclusion, only a few dietary determinants of Hb-AA and Hb-GA were identified. Thus, the present study implies that dietary intake measured by an FFQ explains only to a limited extent the variation in Hb-AA and Hb-GA concentrations.

Diets higher in protein content result in increased satiety and energy expenditure. In the short term, gelatin showed stronger hunger suppression and less subsequent energy intake compared with other proteins. The present study investigated whether a supra-sustained gelatin–milk protein (GMP) diet promotes weight loss compared with a sustained milk protein (SMP) diet and a supra-sustained milk protein (SSMP) diet during an 8-week diet period. A total of seventy-two healthy subjects (31·2 (sd 4·8) kg/m2; 43 (sd 10) years) followed one of the three diets in a subject-specific amount: SMP, SSMP or GMP diet. During weeks 1–4, energy intake was 100 % of individual energy requirement: 10, 40 and 50 % of energy (En %) as protein, fat and carbohydrate, respectively (SMP diet), and 20, 30 and 50 En % as protein, fat and carbohydrate, respectively (SSMP diet or GMP diet). During weeks 5–8, energy intake was 33 % of individual energy requirement: 30, 35 and 35 En % as protein, fat and carbohydrate, respectively (SMP diet), and 60, 5 and 35 En % as protein, fat and carbohydrate, respectively (SSMP diet or GMP diet). Thus, absolute protein intake was kept constant throughout per subject. Significant decreases in BMI (P < 0·0001) were similar between the GMP ( − 1·7 (sd 0·5) kg/m2) and the SMP ( − 2·1 (sd 0·8) kg/m2) and SSMP ( − 1·6 (sd 0·5) kg/m2) diets. Decreases in fat-free mass (FFM), fat mass (FM) and FM %, and increases in FFM % were similar between the GMP and both control diets. Changes in RQ differed (P < 0·05) between the GMP ( − 0·01 (sd 0·06)) and SSMP ( − 0·04 (sd 0·04)) diets. Changes in HDL concentrations differed (P < 0·05) between the GMP ( − 0·21 (sd 0·18) mmol/l) and the SMP and SSMP diets ( − 0·08 (sd 0·18) mmol/l and − 0·09 (sd 0·26) mmol/l, respectively). In conclusion, a gelatin–milk protein diet does not induce more beneficial effects during an 8-week weight-loss period compared with a SMP or SSMP diet.

There is debate over the casual factors for the rise in body weight in the UK. The present study investigates whether increases between 1986 and 2000 for men and women were a result of increases in mean total energy intake, decreases in mean physical activity levels or both. Estimates of mean total energy intake in 1986 and 2000 were derived from food availability data adjusted for wastage. Estimates of mean body weight for adults aged 19–64 years were derived from nationally representative dietary surveys conducted in 1986–7 and 2000–1. Predicted body weight in 1986 and 2000 was calculated using an equation relating body weight to total energy intake and sex. Differences in predicted mean body weight and actual mean body weight between the two time points were compared. Monte Carlo simulation methods were used to assess the stability of the estimates. The predicted increase in mean body weight due to changes in total energy intake between 1986 and 2000 was 4·7 (95 % credible interval 4·2, 5·3) kg for men and 6·4 (95 % credible interval 5·9, 7·1) kg for women. Actual mean body weight increased by 7·7 kg for men and 5·4 kg for women between the two time points. We conclude that increases in mean total energy intake are sufficient to explain the increase in mean body weight for women between 1986 and 2000, but for men, the increase in mean body weight is likely to be due to a combination of increased total energy intake and reduced physical activity levels.

Maternal malnutrition during lactation programmes for overweight and central leptin resistance in adulthood. The inhibition of lactation by maternal treatment with bromocriptine (a prolactin inhibitor) programmes for obesity, hyperleptinaemia and leptin resistance. Here, we evaluated the short- and long-term effects of early weaning (EW) on body-weight regulation, leptin signalling, and hormone and lipid profiles in rats offspring. Lactating rats were separated into two groups: EW – dams were wrapped with a bandage to interrupt the lactation in the last 3 d of lactation; control – dams whose pups had free access to milk during all lactation (21 d). Data were significant at P < 0·05. At weaning, EW pups presented lower body weight ( − 10 %), length ( − 4 %), visceral fat ( − 40 %), total fat ( − 30 %), serum leptin ( − 73 %), glycaemia ( − 10 %), serum insulin ( − 20 %) and insulin resistance index (IRI; − 30 %), but higher total body protein content (+40 %). At 180 d, EW offspring showed hyperphagia, higher length (+3 %), body weight (+8 %), visceral and total fat (+36 and 84 %), serum TAG (+96 %), glycaemia (+15 %), leptinaemia (+185 %) and IRI (+29 %); however, they showed lower total protein content ( − 23 %), leptin:body fat ratio (41 %), prolactinaemia ( − 38 %) and adiponectinaemia ( − 59 %). Despite unchanged leptin receptor (OB-R) and signal transducer and activator of transcription 3 (STAT3), they displayed lower hypothalamic janus tyrosine kinase 2, phosphorylated STAT3 and a higher suppressor of cytokine signalling 3 levels, suggesting a central leptin resistance. Adult rats that were early weaned displayed higher adiposity, insulin resistance and dyslipidaemia, which are related to metabolic syndrome development. Our model reinforces the idea that neonatal malnutrition caused by shortening of the lactation period is important for metabolic programming of future diseases.