Conjugated linoleic acids (CLA) are biologically highly active lipid compounds that inhibit the development of atherosclerotic plaques in experimental animals. The underlying mechanisms of action, however, are only poorly understood. Since cell-culture experiments are appropriate to provide a detailed view into the mechanisms of action of a compound, the present review summarises results from in vitro studies dealing with the effects of CLA isomers and CLA mixtures on functional properties of cells of the vascular wall, such as endothelial cells, smooth muscle cells and monocyte-derived macrophages, which are amongst the major cells contributing to atherosclerotic lesion development. Based on these studies, it can be concluded that CLA exert several beneficial actions in cells of the vascular wall through the activation of nuclear PPAR. These actions of CLA, which may, at least partially, explain the inhibition of atherogenesis by dietary CLA, include modulation of vasoactive mediator release from endothelial cells, inhibition of inflammatory and fibrotic processes in activated smooth muscle cells, abrogation of inflammatory responses in activated macrophages, and reduction of cholesterol accumulation in macrophage-derived foam cells.

The infant born small size for gestational age (SGA) has low bone mass. Since dietary arachidonic acid (AA) and DHA enhance bone mass in normal-birth-weight piglets the objective of the present study was to test for such benefits in the SGA piglet. In the present 15 d study, two levels of dietary AA and DHA (6:1 ratio of AA:DHA diets, 0·6:0·1 or 1·2:0·2 g/100 g dietary fat) v. a control diet were tested for effects on growth, fatty acid status, whole-body and regional bone mineral content (BMC) and metabolism in SGA piglets categorised as either very low birth weight (VLBW; ≤ 1·0 kg; n 12) or low birth weight (LBW; 1·1 to 1·2 kg; n 18). Differences in outcomes for each body weight category were detected using ANOVA with post hoc Bonferroni tests. Growth was not influenced by diet, yet the LBW piglets fed 0·6:0·1 AA and DHA as g/100 g fat had elevated BMC in the spine, whereas the VLBW piglets had higher BMC of the spine if fed the higher intake of AA and DHA. In both weight categories, the higher intake of AA and DHA lowered bone resorption relative to controls, whereas bone formation was unchanged. Tissue fatty acid concentrations reflected dietary AA and DHA, especially trabecular bone of VLBW piglets. Whether the enhanced lumbar spine BMC is due to enhanced Ca absorption and thus suppression of bone resorption remains to be established.

The risk of Alzheimer's disease is increased for carriers of apoE4 (E4) or the PPAR-α L162V polymorphism (L162V), but it is decreased in fish and seafood consumers. The link between high fish intake and reduced risk of cognitive decline in the elderly appears not to hold in carriers of E4, possibly because better cognition is linked to EPA+DHA in the blood, but only in non-carriers of E4. As yet, no such studies exist in carriers of L162V. Our objective was to determine whether the plasma fatty acid response to a dietary supplement of EPA+DHA was altered in carriers of L162V and/or E4. This was an add-on project; in the original study, men were selected based on whether or not they were carriers of L162V (n 14 per group). E4 status was determined afterwards. All subjects received an EPA+DHA supplement for 6 weeks. L162V polymorphism did not interact with the supplement in a way to alter EPA and DHA incorporation into plasma lipids. However, when the groups were separated based on the presence of E4, baseline EPA and DHA in plasma TAG were 67 and 60 % higher, respectively, in E4 carriers. After the supplementation, there were significant gene × diet interactions in which only non-carriers had increased EPA and DHA in plasma NEFA and TAG, respectively.

The NADPH oxidase enzyme system is the main source of superoxide anions in phagocytic and vascular cells. NADPH oxidase-dependent superoxide generation has been found to be abnormally enhanced in several chronic diseases. Evidence is accumulating that polyphenols may have the potential to improve cardiovascular health, although the mechanism is not fully established. Consumption of concentrated red grape juice, rich in polyphenols, has been recently shown to reduce NADPH oxidase activity in circulating neutrophils from human subjects. In the present work we studied whether red grape juice polyphenols affected NADPH oxidase subunit expression at the transcription level. For this, we used human neutrophils and mononuclear cells from peripheral blood, HL-60-derived neutrophils and the endothelial cell line EA.hy926.Superoxide production was measured with 2′7′-dichlorofluorescein diacetate or lucigenin, mRNA expression by real-time RT-PCR and protein expression by Western blot. Each experiment was performed at least three times. In all cell types tested, red grape juice, dealcoholised red wine and pure polyphenols decreased superoxide anion production. Red grape juice and dealcoholised red wine selectively reduced p47phox, p22phox and gp91phox expression at both mRNA and protein levels, without affecting the expression of p67phox. Pure polyphenols, particularly quercetin, also reduced NADPH oxidase subunit expression, especially p47phox, in all cell types tested. The present results showing that red grape juice polyphenols reduce superoxide anion production provide an alternative mechanism by which consumption of grape derivatives may account for a reduction of oxidative stress associated with cardiovascular and/or inflammatory diseases related to NADPH oxidase superoxide overproduction.

The objective of the present study was to measure the differences in body composition, adipose tissue gene expression, blood metabolite and hormone concentrations, and insulin sensitivity in kittens exposed to high-protein (HP) or high-carbohydrate (HC) nutrition in utero and through the growth period. Eight dams were randomised onto two test diets, and fed the diets throughout gestation and lactation. Male offspring were evaluated for 9 months. Kittens were weaned at 2 months of age onto the same treatment diet as the dam and were allowed to consume diets ad libitum. The HC diet contained 34·3 % crude protein (CP), 19·2 % fat and 30·8 % digestible carbohydrate, while the HP diet contained 52·9 % CP, 23·5 % fat and 10·8 % digestible carbohydrate. Blood samples were collected at 6 months after birth. Body composition was determined at 2 and 8 months of age and an intravenous glucose tolerance test, neutering and adipose tissue biopsy conducted at 8 months of age. Physical activity was quantified at 6 and 9 months. Energy intake, DM intake and body weight were not different between groups. At 2 months, blood TAG were greater (P < 0·05) in kittens fed the HP diet. At 8 months, blood leptin was higher (P < 0·05) in kittens fed the HC diet, while chemokine receptor 5, hormone-sensitive lipase, uncoupling protein 2, leptin and insulin receptor mRNA were greater (P < 0·05) in kittens fed the HP diet. The present results demonstrate some of the changes in blood metabolites and hormones, physical activity and mRNA abundance that occur with feeding high protein levels to kittens.

Propionyl-l-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200 mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of l-carnitine supplements on metabolic disorders.

Diet influences the composition of the gut microbiota and host's health, particularly in patients suffering from food-related diseases. Coeliac disease (CD) is a permanent intolerance to cereal gluten proteins and the only therapy for the patients is to adhere to a life-long gluten-free diet (GFD). In the present preliminary study, the effects of a GFD on the composition and immune function of the gut microbiota were analysed in ten healthy subjects (mean age 30·3 years) over 1 month. Faecal microbiota was analysed by fluorescence in situ hybridisation (FISH) and quantitative PCR (qPCR). The ability of faecal bacteria to stimulate cytokine production by peripheral blood mononuclear cells (PBMC) was determined by ELISA. No significant differences in dietary intake were found before and after the GFD except for reductions (P = 0·001) in polysaccharides. Bifidobacterium, Clostridium lituseburense and Faecalibacterium prausnitzii proportions decreased (P = 0·007, P = 0·031 and P = 0·009, respectively) as a result of the GFD analysed by FISH. Bifidobacterium, Lactobacillus and Bifidobacterium longum counts decreased (P = 0·020, P = 0·001 and P = 0·017, respectively), while Enterobacteriaceae and Escherichia coli counts increased (P = 0·005 and P = 0·003) after the GFD assessed by qPCR. TNF-α, interferon-γ, IL-10 and IL-8 production by PBMC stimulated with faecal samples was also reduced (P = 0·021, P = 0·037, P = 0·002 and P = 0·007, respectively) after the diet. Therefore, the GFD led to reductions in beneficial gut bacteria populations and the ability of faecal samples to stimulate the host's immunity. Thus, the GFD may constitute an environmental variable to be considered in treated CD patients for its possible effects on gut health.

A randomised, parallel-design dietary intervention study was conducted in women (aged 45–75 years) with prehypertension or stage 1 hypertension. The aim was to compare the effects on bone turnover of a low-Na base-producing (LNAB) Dietary Approaches to Stop Hypertension (DASH)-type diet (including six serves lean red meat/week) with a high-carbohydrate low-fat (HCLF) diet with a higher acid load (both >800 mg dietary Ca/d). Fasting serum bone markers (baseline and week 14) and 24 h urinary electrolyte excretion (baseline, weeks 4, 8, 12 and 14) were measured. After the intervention period, the LNAB group (n 46) had a fall of 26 (sem 6) % (P < 0·0001) in urinary Na, an increase in K excretion (6·8 (sem 3·6) mmol/d; P = 0·07) and, compared with the HCLF group (n 49), a greater reduction in urinary Ca excretion by 0·7 (sem 0·3) mmol/d. Serum 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin did not change, and both groups had a similar increase of 23 (sem 5) % (P < 0·0001) in C-terminal telopeptide of type I collagen. The HCLF group had an 11 (sem 4) % increase (P = 0·003) in N-terminal propeptide, type I procollagen, which could indicate an increased rate of bone turnover. The fall in urinary Ca with the lower-Na lower-acid load diet is likely to have long-term beneficial effects on bone. As bone resorption was not different between the two dietary patterns with relatively high Ca intake, the effect on bone health of a dietary pattern with a lower acid load warrants further study on a lower Ca intake.

Vitamin K contributes to bone health, probably through its role as cofactor in the carboxylation of osteocalcin. Intervention studies in adults have demonstrated that markedly higher osteocalcin carboxylation is obtained by intakes of vitamin K well above the current recommended dietary intake. However, the relationship between increased vitamin K2 intake and enhanced osteocalcin carboxylation has never been shown in healthy children. The objective was to study the effect of 45 μg menaquinone-7 (MK-7; one of the vitamin K2 species) on the circulating levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (cOC) in healthy prepubertal children. We hypothesised that MK-7 supplementation will reduce the ucOC:cOC ratio (UCR), indicating an improved vitamin K status. The present study is a double-blind randomised placebo-controlled trial examining the effect of 8 weeks MK-7 supplementation on the carboxylation of osteocalcin in healthy children (n 55). Serum levels of ucOC, cOC and MK-7 were measured at baseline and after 8 weeks, together with bone markers and coagulation parameters. The UCR was used as an indicator of vitamin K status. In the MK-7-supplemented group (n 28), the circulating concentration of inactive ucOC reduced and the UCR improved whereas the concentration of MK-7 increased. Within the placebo group, ucOC, cOC, UCR and MK-7 did not significantly change over time. In both groups, bone markers and coagulation parameters remained constant over time. These findings demonstrate that in healthy, prepubertal children, modest supplementation with MK-7 increases circulating concentrations of MK-7 and increases osteocalcin carboxylation.

Postnatal growth failure in preterm infants is due to interactions between genetic and environmental factors, which are not fully understood. We assessed dietary supply of nutrients in very-low-birth-weight (VLBW, < 1500 g) infants fed fortified human milk, and examined the association between nutrient intake, medical factors and growth during hospitalisation lasting on average 70 d. We studied 127 VLBW infants during the early neonatal period. Data were obtained from medical records on nutrient intake, growth and growth-related factors. Extra-uterine growth restriction was defined as body weight < 10th percentile of the predicted value at discharge. Using logistic regression, we evaluated nutrient intake and other relevant factors associated with extra-uterine growth restriction in the subgroup of VLBW infants with adequate weight for gestational age at birth. The proportion of growth restriction was 33 % at birth and increased to 58 % at discharge from hospital. Recommended values for energy intake (>500 kJ/kg per d) and intra-uterine growth rate (15 g/kg per d) were not met, neither in the period from birth to 28 weeks post-conceptional age (PCA), nor from 37 weeks PCA to discharge. Factors negatively associated with growth restriction were energy intake (Ptrend = 0·002), non-Caucasian ethnicity (P = 0·04) and weight/predicted birth weight at birth (Ptrend = 0·004). Extra-uterine growth restriction is common in VLBW infants fed primarily fortified human milk. Currently recommended energy and nutrient intake for growing preterm infants was not achieved. Reduced energy supply and non-Caucasian ethnicity were risk factors for growth restriction at discharge from hospital.

Green tea may stimulate energy metabolism; however, it is unclear if acute effects are caused by specific catechins, caffeine or their combination. The objective of the present study was to examine the separate and combined effects of different catechins and caffeine on energy expenditure (EE) and fat oxidation over a single day. Fifteen healthy, normal-weight males received capsules containing placebo, caffeine alone (150 mg), or caffeine plus a catechin mixture (600 mg) enriched in either epigallocatechin-3-gallate (EGCG), epigallocatechin or a mix of catechins, in a randomised cross-over double-blinded design. On each test day EE, respiratory quotient (RQ) and substrate oxidation were measured under sedentary conditions in a respiratory chamber for 13·5 h. We found no significant treatment effect on EE (P = 0·20) or RQ (P = 0·68). EGCG with caffeine insignificantly raised EE and fat oxidation v. caffeine-only and placebo (EE 5·71 (se 0·12) v. 5·68 (se 0·14) v. 5·59 (se 0·13) MJ/12·5 h, respectively; fat oxidation 84·8 (se 5·2) v. 80·7 (se 4·7) v. 76·8 (se 4·0) g/12·5 h). Catechin/caffeine combinations at these dosages and mode of application had non-significant acute effects on EE and fat oxidation. The maximum observed effect on EE of about 2 % could still be meaningful for energy balance over much longer period of exposure. However, higher short-term effects reported in the literature may reflect variations in green tea extracts, added caffeine, or synergies with physical activity. The specific mechanisms and conditions that may underpin observed longer-term benefits of catechin-enriched green tea consumption on body composition remain to be confirmed.

Few studies have investigated the absorption of phylloquinone (vitamin K1). We recruited twelve healthy, non-obese adults. On each study day, fasted subjects took a capsule containing 20 μg of 13C-labelled phylloquinone with one of three meals, defined as convenience, cosmopolitan and animal-oriented, in a three-way crossover design. The meals were formulated from the characteristics of clusters identified in dietary pattern analysis of data from the National Diet and Nutrition Survey conducted in 2000–1. Plasma phylloquinone concentration and isotopic enrichment were measured over 8 h. Significantly more phylloquinone tracer was absorbed when consumed with the cosmopolitan and animal-oriented meals than with the convenience meal (P = 0·001 and 0·035, respectively). Estimates of the relative availability of phylloquinone from the meals were: convenience meal = 1·00; cosmopolitan meal = 0·31; animal-oriented meal = 0·23. Combining the tracer data with availability estimates for phylloquinone from the meals provides overall relative bioavailability values of convenience = 1·00, cosmopolitan = 0·46 and animal-oriented = 0·29. Stable isotopes provide a useful tool to investigate further the bioavailability of low doses of phylloquinone. Different meals can affect the absorption of free phylloquinone. The meal-based study design used in the present work provides an approach that reflects more closely the way foods are eaten in a free-living population.

Isoflavone (IFL) intake may provide numerous health benefits, but IFL bioavailability differences among soya foods remains uncertain. Urinary IFL excretion (UIE) was shown to provide a reliable surrogate for systemic IFL exposure and therefore can be used as a measure of ‘apparent bioavailability’ (AB). We investigated the AB of IFL in fourteen healthy adults, consuming two liquid and two solid soya foods in a crossover designed study. Volunteers consumed the foods with a self-selected breakfast, which was kept identical for all four soya items (soya nuts, soya milk, soya protein bar and soya protein powder drink in water; average 23·7 mg IFL, 88–96 % glycosides, by HPLC analysis) and collected all urine up to 26 h. Liquid foods showed initially higher UIE values than solid foods, but this difference was considerably reduced or disappeared entirely after 24–26 h. Conclusive AB results were obtained only after 24–26 h; earlier collections were not reliable. At 26 h, adjusted UIE values for daidzein (DE) were 20 μmol in the milk and bar and 17 μmol for the nut and powder; urinary genistein excretion was the highest in the milk group (10 μmol) followed by the nut, bar (both 6 μmol) and powder groups (5 μmol); the UIE for glycitein was the highest for bars (4 μmol), followed by powder and nuts (3 μmol), and milk (2 μmol). DE makes the largest contribution to urinary total IFL. The AB of IFL was found to be variable depending on the analyte and soya food consumed.

Previous studies have indicated low serum carotenoid concentrations among cigarette smokers and/or alcohol drinkers, but little is known about the interaction of smoking and drinking with serum carotenoids. We tested the hypothesis that smoking and drinking reduce serum carotenoid concentrations synergistically. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. The subjects were divided into six groups according to alcohol intake (non-drinkers, < 1 g/d; light drinkers, ≥ 1, < 25 g/d; moderate-to-heavy drinkers, ≥ 25 g/d) and smoking status (non-smokers and current smokers). The dietary intakes and serum concentrations of six carotenoids (lycopene, α-carotene, β-carotene, lutein, β-cryptoxanthin and zeaxanthin) within each group were evaluated cross-sectionally. The dietary intakes of all carotenoids did not differ in the six groups after adjusting for age and sex. The multivariate-adjusted means of the serum carotenoid concentrations in non-drinkers did not differ between non-smokers and current smokers. In contrast, the adjusted means of serum α-carotene, β-carotene and β-cryptoxanthin were significantly lower than those with increased alcohol intake, and these lower serum carotenoids among alcohol drinkers were more evident in current smokers than in non-smokers. Serum lycopene of moderate-to-heavy drinkers was significantly lower than that of non-drinkers, but it was not influenced by smoking. Neither smoking nor drinking was associated with the serum concentrations of lutein and zeaxanthin. These results suggest that smoking and drinking may reduce the serum α-carotene, β-carotene and β-cryptoxanthin concentrations in a synergistic manner.

The validity of self-reported dietary intake is critical to the design and interpretation of diet–disease investigations. For many nutrients, there are no ideal methods to establish validity, given correlated error between reference and assessment tools, and constraints on time and resources available to perform such studies. Therefore, we quantified associations between macronutrient intakes and plasma HDL-cholesterol and TAG, relying on known associations between these factors to test the criterion validity of the FFQ used in the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline dietary macronutrient intakes (derived from 120-item FFQ), and fasting plasma HDL and TAG were measured in 4510 MESA participants, aged 45–84 years. After adjusting for non-dietary factors known to affect plasma lipid concentrations, greater carbohydrate intake was associated with lower HDL and higher TAG (β per 5-unit change in percentage energy intake from carbohydrate = − 5 (se 1) mg/l (P < 0·001) for HDL and 15 (se 6) mg/l (P = 0·008) for TAG), whereas higher energy intake from fat was associated with higher HDL and lower TAG (β per 5-unit change in percentage energy from fat = 3·7 (se 2) mg/l (P = 0·01) for HDL and β = 19 (se 7) mg/l (P = 0·004) for TAG). Associations of dietary carbohydrate and fat intakes with HDL and TAG concentrations were consistent with previous studies, demonstrating criterion validity of these dietary measures in the MESA.

Intake in the morning is associated with a reduction in the total intake for the day, while intake at night is associated with greater overall daily intake. These associations are macronutrient specific, with morning carbohydrate intake associated with reduced daily carbohydrate intake, morning fat intake associated with reduced daily fat intake and morning protein intake associated with reduced daily protein intake. Since different types of foods contain differing proportions of macronutrients, the present study investigated the associations of different types of foods ingested at various times of day with total daily and macronutrient intakes. The intakes of 388 male and 621 female free-living individuals reported in 7 d diet diaries were reanalysed. The intakes of twenty-four different types of foods and seven different drinks occurring during the morning (04.00–10.29 hours), afternoon (10.30–16.59 hours) and evening (17.00–02.00 hours) were identified and related to overall daily intakes. Dairy foods, ice cream, beef, other meats, potatoes, pastry, nuts, chips and snacks, condiments, alcohol and soda were significantly associated with higher total intake over the day, while fruit, soup, breakfast cereal, pasta, pizza, water, coffee/tea and diet soda were either not associated or were associated with lower overall intake. Dietary energy density appeared to mediate the associations between particular foods and beverages and overall energy intake. This suggests that eating low-density foods in the morning and avoiding high-density foods at night might aid in reducing overall intake and may be useful in dietary interventions for overweight and obesity.

Over a decade ago, the finding of a form of low-grade systemic inflammation (‘metaflammation’) associated with obesity, insulin resistance and chronic disease proffered a causal explanation for the latter. However, recent work has shown that metaflammation is also associated with several modern lifestyle-related and environmental inducers, with or without obesity. Here, we present accumulating data to show a link between metaflammation and a number of non-microbial environmental and lifestyle stimulants, both with and without obesity. This implies that obesity may often be an accomplice to, as much as an offender in, major metabolic disease. The real (albeit distal) cause of such a disease appears to lie in aspects of the modern techno-industrial environment driving unhealthy lifestyle behaviours. If true, this suggests that while individual weight loss may be a component of chronic disease management, it may be neither ‘necessary’ nor ‘sufficient’ to reduce the problem at a population level. Greater multidisciplinary and policy input is needed to modify the economic and political drivers of the modern, obesogenic environment.