Central nervous system leptin resistance as a possible cause of obesity and associated diseases is a ‘hot topic’ in nutrition research. Simultaneously, a new field in biomedical sciences has evolved during the past years.

Folic acid plays an essential role in DNA and methionine metabolism. Micro-organisms in the rumen can synthesise folates, but it has not been verified that these amounts are sufficient to achieve the best efficiency of dairy cows. However, the amount of folates synthesised in the rumen could possibly, to some extent, be affected by the forage:concentrate ratio. Degradation of orally supplemented folic acid in the rumen seems to be very high (about 97 %), as supplementation of folic acid hardly increases folate concentrations in the digesta at the duodenum. However, it must be considered that dietary supplements of folic acid higher than 0·5 mg/kg body weight increased serum folate concentrations in all available studies and milk folate concentrations in most studies. Additionally, milk production tended to be increased in some studies. Therefore, degradation of folic acid in the rumen may be overestimated as folates can be absorbed at the proximal duodenum. For future research it is necessary to consider the whole flow and the metabolic pathways of folates from the rumen to duodenum, blood, tissue, milk and transfer to calf to declare requirement values for cows. Consequently, the present review discusses current knowledge and emphasises areas for future research.

It is not known whether trace amounts of proteins that may remain in cereal-starch-derived food ingredients even after food processing can trigger allergic symptoms in cereal-allergic individuals. The aim of this study was to find out if barley starch syrup causes allergic reactions in patients with allergy to wheat, barley, rye or oats. Fifteen children with allergy to these cereals, confirmed by double-blind placebo-controlled food challenge (DBPCFC), were selected for the study. When exposed to cereals, seven of the children (47 %) showed immediate type reactions, such as urticaria, rash or anaphylaxis. Eight of the children (53 %) showed delayed type reactions, such as deterioration of atopic dermatitis or diarrhoea. The fifteen children with allergy to cereals were exposed to barley starch syrup in DBPCFC and none of them showed any objective signs of allergy. On skin-prick tests (SPT), five of the children (33·3 %) showed a positive ( ≥ 3 mm) reaction to at least one of the cereals but none of them to barley starch syrup. This study confirmed with 98 % confidence that at least 90 % of the patients with verified allergy to cereals will not react with allergic symptoms to barley starch syrup.

Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Multidrug resistance gene-deficient (mdr1a− / − ) mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet–gene interactions and potential effects of foods on remission or development of IBD. The present study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a− / −  mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets (control (AIN-76A), control +0·2 % curcumin or control +0·1 % rutin) and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a− / −  mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways, probably mediated by pregnane X receptor (Pxr) and peroxisome proliferator-activated receptor α (Ppara) activation of retinoid X receptor (Rxr). These results indicate the potential of global gene expression and pathway analyses to study and better understand the effect of foods in modulating colonic inflammation.

Selenium is an important trace element with anti-cancer properties. In the present study, the apoptosis-inducing effects of organic selenium derivatives, namely methyl-l-selenocysteine and selenomethionine, were evaluated in vitro on human tumour-derived cell lines from breast, liver, colon, brain, skin and a non-tumorigenic line of epithelial origin. Apoptosis was assessed by cell-death detection immunoassay on cytoplasmic cell lysates. Breast carcinoma cells were highly sensitive to the organic selenium compounds, manifesting apoptosis at concentrations as low as 0·113 μm (0·0205 μg/ml) selenium. By contrast, non-tumorigenic mammary epithelial cells displayed poor sensitivity to selenium, requiring a substantially high concentration of the trace element of 87·9 μm (16·0 μg/ml). The cell lines derived from hepatoma and neuroblastoma showed intermediate sensitivity, with colon carcinoma cells manifesting the lowest sensitivity to the trace element. These results indicate intrinsic differences in the sensitivity of human tumour derivatives to selenium-mediated apoptosis, providing experimental support for the development of organic selenium compounds as anti-neoplastic agents against solid tumours displaying selective apoptotic sensitivity to these compounds.

This study was performed to investigate whether dietary lysine concentration influences the carnitine status of pigs. Therefore, an experiment with twenty young pigs with an average body weight of 21 kg was performed which were fed either a control diet (9·7 g lysine/kg) or a diet with a moderate excess of lysine (16·8 g lysine/kg). Concentrations of all the other amino acids did not differ between the diets. Pigs fed the high-lysine diet had lower concentrations of free and total carnitine in plasma, liver, kidney and skeletal muscle than control pigs (P < 0·05). Pigs fed the high-lysine diet moreover had an increased concentration of trimethyllysine (TML), a reduced mRNA abundance of TML dioxygenase and reduced concentrations of γ-butyrobetaine (BB) in muscle, indicating that the conversion of TML into BB in muscle was impaired. Concentrations of BB, the metabolic precursor of carnitine, in plasma, liver and kidney were also reduced in pigs fed the high-lysine diet while the activity of BB dioxygenase in kidney was not different and that in liver was even increased compared to control pigs (P < 0·05). In conclusion, this study shows that a moderate dietary excess of lysine lowers plasma and tissue carnitine concentrations in pigs. Reduced concentrations of BB in liver and kidney suggest that the depressed carnitine status was likely caused by a decreased rate of carnitine synthesis due to a diminished availability of carnitine precursor, probably mainly as a result of an impaired BB formation in muscle.

The aim of this study was to describe the effects of two diets differing in n-6:n-3 ratio and prepartal feeding regime on gene expression of PPARγ1a/1b, PPARγ1c/1d, PPARγ2, PPARγ coactivator 1A (PPARGC1A), GLUT4, TNFα, adiponectin, leptin, leptin receptor (LEPR), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL) in sows' white adipose tissue on the first day of lactation. The relationship between mRNA expression of these genes and circulating insulin, leptin and thyroid hormones was also considered. Diets contained a low (supplemented with fish oil; f group) or a high (supplemented with sunflower oil; s group) n-6:n-3 ratio and were provided from 8 (f8, s8) or 3 d (f3, s3) before parturition (onset day 8 or 3). A low n-6:n-3 ratio reduced the 1 d postpartum expression of PPARγ2 and PPARGC1A but only when applied from 3 d before parturition. Circulating leptin was negatively correlated with mRNA expression of adiponectin, LEPR and LPL, whereas thyroxine was positively correlated with levels of PPARGC1A. In conclusion, the effect of dietary treatments, e.g. altering the n-6:n-3 ratio, around parturition on the expression of crucial genes in nutrient metabolism can be modulated by the duration of application before parturition.

There are few good sources of natural food folates apart from green leafy vegetables and these may have a limited potential to increase folate status because of substantial losses that can occur during cooking. Fortified foods can overcome this but are controversial because of safety concerns regarding chronic exposure to high-dose folic acid (FA; the synthetic form). The aim of the present study was to develop eggs with an enriched natural folate content and minimal unmetabolised FA. Forty-eight, 30-week-old laying hens were randomised to receive the basal feed (formulated to provide 1 mg folate/kg feed) to which had been added one of the following FA levels (0, 2, 4, 8, 16, 32 mg/kg feed). Total folate was measured in eggs collected throughout the 12-week study period and the FA content estimated at 12 weeks. Results showed that the maximal egg folate content was achieved by adding 16 mg FA/kg feed. At this optimal dose, the total folate content per egg was 75 μg (compared with 32 μg in a regular egg) of which FA represented at most 10 %, a level which would probably be converted into natural folates by humans after ingestion. The results demonstrate that it is possible to use synthetic FA at high doses to produce novel animal foods enriched with natural folates in a cost-efficient process. Such foods may be particularly relevant to European populations without access to FA fortification and therefore dependent on natural food folate sources for the primary prevention of folate-related disease.

Based on the potential benefits to long-term human health there is interest in developing sustainable nutritional strategies for reducing saturated and increasing specific unsaturated fatty acids in ruminant milk. The impact of plant oil supplements to diets containing different forages on caprine milk fatty acid composition was examined in two experiments using twenty-seven Alpine goats in replicated 3 × 3 Latin squares with 28 d experimental periods. Treatments comprised of no oil (control) or 130 g/d of sunflower-seed oil (SO) or linseed oil (LO) supplements added to diets based on grass hay (H; experiment 1) or maize silage (M; experiment 2). Milk fat content was enhanced (P < 0·01) on HSO, HLO and MLO compared with the corresponding H or M control diets, resulting in 17, 15 and 14 % increases in milk fat secretion, respectively. For both experiments, plant oils decreased (P < 0·05) milk 10 : 0–16 : 0 and odd- and branched-chain fatty acid content and increased 18 : 0, trans-Δ6–9,11–14,16-18 : 1 (and their corresponding Δ-9 desaturase products), trans-7, trans-9-conjugated linoleic acid (CLA), trans-9, trans-11-CLA and trans-8, cis-10-CLA concentrations. Alterations in the distribution of cis-18 : 1, trans-18 : 1, -18 : 2 and CLA isomers in milk fat were related to plant oil composition and forage in the diet. In conclusion, plant oils represent an effective strategy for altering the fatty acid composition of caprine milk, with evidence that the basal diet is an important determinant of ruminal unsaturated fatty acid metabolism in the goat.

We evaluated the effect of undegradable intake protein (UIP) on urea kinetics and microbial incorporation of urea-N in ruminally and duodenally fistulated steers (n 4; 319 kg) provided ad libitum access to grass hay in a 4 × 4 Latin square. Casein was continuously infused abomasally in amounts of 0, 62, 124 and 186 mg N/kg body weight per d to simulate provision of UIP. Periods were 13 d long with 7 d for adaptation and 6 d for collection. Jugular infusion of [15N15N]urea followed by determination of urinary enrichment of [15N15N]urea and [14N15N]urea was used to measure urea kinetics. Forage and N intake increased (quadratic, P < 0·02) with increasing UIP. Urea synthesis was 27·1, 49·9, 82·2 and 85·8 g urea-N/d for 0, 62, 124 and 186 diets, respectively (linear, P < 0·01). The proportion of urea synthesis that entered the gastrointestinal tract was 0·96 for steers receiving no UIP and decreased linearly (P = 0·05) to a low of 0·89 for steers receiving 186. The amount of urea entering the gastrointestinal tract was least for 0 (26·3) and increased (linear, P < 0·01) to 48·7, 77·2 and 76·6 g urea-N/d for 62, 124 and 186 diets, respectively. Microbial incorporation of recycled urea-N increased quadratically (P = 0·04) from 13·9 for 0 to 47·7 g N/d for 124. The proportion of microbial N derived from recycled urea increased (quadratic, P = 0·05) from 0·31 to 0·58 between 0 and 124 and dropped to 0·44 for 186 mg N/kg body weight per d. UIP increased intake of hay and provided a N source for ruminal microbes via urea recycling.

Dried plums are a fruit high in pectin with substantial antioxidant activity. Previous studies in rats and man indicate that dried plums or plum fibre lower liver and plasma cholesterol, respectively. The apoE-deficient mouse, which develops atherosclerotic lesions rapidly when fed cholesterol, was used to determine the ability of dried plums to reduce atherosclerosis. Diets containing 0·15 % cholesterol and either 0 (B+C), 4·75 % (Lo DP) or 9·5 % (Hi DP) dried plum powder were fed for 5 months. An additional group fed the basal diet without cholesterol (B − C) was included as a negative control. Arterial trees were dissected, stained to visualize lesions, and lesion area was quantitated by imaging software. Urinary thiobarbituric acid-reactive substances (TBARS) excretion and serum amyloid P-component (SAP) were measured as indicators of oxidative stress and inflammation, respectively. Final serum cholesterol was significantly increased and serum TAG decreased in the B+C group and dried plum groups relative to the B − C group. Percentage arterial tree atherosclerotic lesion area was significantly lower in the B − C and Lo DP groups compared to the B+C group (P < 0·05), with a trend for a difference between the B+C and Hi DP groups (P = 0·075). SAP concentration was significantly lower in the B − C and Lo DP groups with the Hi DP group trending lower than the B+C group. Urinary TBARS excretion did not differ among the groups. These results suggest that consuming dried plums may help slow the development of atherosclerosis.

Eighty-eight multiparous sows were used to evaluate whether type and timing of oil supplementation during gestation influences the incidence of low birth weight (LBW). Sows were allocated (eight per treatment) commercial sow pellets (3 kg/d; control diet) or an experimental diet consisting of control diet plus 10 % extra energy in the form of excess pellets, palm oil, olive oil (OO), sunflower oil (SO) or fish oil; experimental diets were fed during either the first half (G1) or second half (G2) of gestation. Growth performance and endocrine profile of LBW ( < 1·09 kg) and normal birth weight (NBW; 1·46–1·64 kg) offspring were compared. Maternal dietary supplementation altered the distribution curve for piglet birth weight. SOG1 sows had a greater proportion of LBW piglets (P < 0·05), whilst it was reduced in the OOG1 group (P < 0·05). Growth rate of LBW piglets was lower compared with their NBW siblings (P < 0·05) when dietary supplementation was offered in G2 but were similar for G1. At birth, LBW offspring of supplemented animals possessed more fat compared with the control group (P < 0·05); LBW offspring of control animals exhibited a more rapid decline in fat free mass/kg prior to weaning. Plasma metabolites and insulin concentrations were influenced by maternal diet and birth weight. In conclusion, maternal dietary supplementation altered the distribution of piglet birth weights and improved the energy status of LBW piglets. Supplementation with MUFA during G1 reduced the incidence of LBW, whereas PUFA had the reverse effect.

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 μg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (+42·5 %) and lower levels of serum adiponectin ( − 43·2 %). The hypothalamic expression of OB-Rb was lower ( − 22 %) and SOCS-3 was higher (+52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

Polycyclic aromatic hydrocarbons (PAH) are established cancer initiators that can be found in our food and environment. Some dietary phytochemicals are strong inhibitors of PAH-induced mutagenesis. The soya isoflavone genistein has been shown previously in our laboratory to be an inhibitor of PAH metabolite binding to DNA. In the present study, we investigated the effect of genistein on oxidative DNA damage induced by PAH in the non-tumorigenic breast cell line MCF10A. 7,12-Dimethyl-benz[a]anthracene (DMBA) can induce expressions of CYP1A1 and CYP1B1 which are known to be responsive to PAH. These enzymes, in turn, will metabolise the PAH into their ultimate carcinogenic forms. Genistein can significantly suppress the expressions within 5 μm. The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment with genistein at 5 or 10 μm could alleviate the damage. In addition to the chelation of DMBA metabolites to DNA, flow cytometry results revealed that oxidation was also a factor of DNA damage. The oxidative DNA damage could be removed by co-treating with 10 μm-genistein. Because no increased oxidative DNA repair was observed, suppression on the cytochrome enzymes appeared to be the underlying mechanism.

Inflammation and endothelial activation are associated with an increased risk of CVD and epidemiological evidence suggests an association between levels of markers of inflammation or endothelial activation and the intake of fruit. Also, vitamin E, a fat-soluble antioxidant, has anti-inflammatory properties. We performed a randomised 2 × 2 factorial, crossover trial to determine the effect of orange and blackcurrant juice (500 ml/d) and vitamin E (15 mg RRR-α-tocopherol/d) supplementation on markers of inflammation and endothelial activation in forty-eight patients with peripheral arterial disease. Patients were randomly allocated to two dietary supplements from the four possible combinations of juice and vitamin E: juice+vitamin E; juice+placebo; reference beverage (sugar drink)+vitamin E; and reference beverage+placebo. The supplementations were given for 28 d, separated by a 4-week wash-out period. Analysis of main effects showed that juice decreased C-reactive protein (CRP) by 11 % and fibrinogen by 3 % while the reference drink increased CRP by 13 % and fibrinogen by 2 % (P < 0·008 and P < 0·002, respectively). No significant differences were measured for IL-6 and the endothelial activation markers von Willebrand factor, tissue-plasminogen activator and plasmin activator inhibitor-1. Vitamin E supplementation had no significant effects on the various markers. We observed no significant interaction between juice and vitamin E. In this study, orange and blackcurrant juice reduced markers of inflammation, but not markers of endothelial activation, in patients with peripheral arterial disease, relative to sugar drinks.

Diabetic retinopathy increases with duration of diabetes and may be associated with carotenoid status. Carotenoids alter the pro-oxidation/antioxidation balance, and circulating levels depend largely on dietary intake. Lower levels have been reported in diabetes and age-related macular degeneration; however, little is known of the relationship between carotenoids and diabetic complications. Consequently, the purpose of the present study was to evaluate the relationship between plasma carotenoids and diabetic retinopathy. We assessed the carotenoid–retinopathy relationship in 111 individuals with type 2 diabetes in a community-based, cross-sectional study. We photodocumented retinal status and used HPLC to measure plasma carotenoid concentrations. Data for clinical and demographic variables and risk factors for diabetic retinopathy were obtained from 24 h urine and fasting blood samples, and an interviewer-assisted lifestyle questionnaire. We found that the combined lycopene and lutein/zeaxanthin (non-pro-vitamin A (non-PVA) carotenoid) concentration when compared with the pro-vitamin A (PVA) carotenoids (α-carotene, β-carotene and β-cryptoxanthin) was significantly lower in the retinopathy than non-retinopathy group (OR 1·2 (95 % CI 1·0, 1·4) v. 1·6 (95 % CI 1·4, 1·7), respectively; P = 0·009). A higher non-PVA:PVA ratio also predicted a lower risk of diabetic retinopathy, after adjustment for potential confounders (OR 0·33 (95 % CI 0·12, 0·95); P = 0·039). Finally, a higher concentration of PVA carotenoids was associated with greater odds of diabetic retinopathy, after adjustment for risk factors (P = 0·049). We suggest synergies between carotenoids are implicated in diabetic retinopathy, independent of established risk factors. Importantly, our observations indicate dietary modulation of retinopathy risk may be possible by increasing intakes of lutein- and lycopene-rich foods.

Serum banks from large, decades-old epidemiological studies provide a valuable opportunity to explore the contributions of in utero vitamin D exposure to fetal origins of adult diseases. We compared 25-hydroxyvitamin D (25(OH)D) by race and season (two powerful predictors of vitamin D status) in sera frozen for ≥  40 years with sera frozen for ≤  2 years to determine whether 25(OH)D is stable enough to test vitamin D-related hypotheses. Data and sera came from seventy-nine pregnant women at 29–32 weeks' gestation in the Boston Collaborative Perinatal Project (CPP; 1959–66) and 124 women at 20–36 weeks' gestation in a 2003–2006 Pittsburgh cohort study. Multivariable linear regression models were used to test main and joint effects of race and season after confounder adjustment. In both cohorts, serum 25(OH)D levels were lower among black than white women (CPP 33·3 v. 46·7 nmol/l, P < 0·01; Pittsburgh 47·1 v. 89·6 nmol/l; P < 0·0001) and in winter than summer (CPP 32·7 v. 47·6 nmol/l, P < 0·0001; Pittsburgh 66·7 v. 89·8 nmol/l, P < 0·001), with no evidence of a race × season interaction in either cohort. Differences remained significant after confounder adjustment. When CPP and Pittsburgh results were compared, there was no significant difference in the race or season effects. The similarity in the relative change in 25(OH)D in these cohorts by two powerful predictors of vitamin D status suggests that, even if 25(OH)D deteriorated somewhat, it did so similarly across samples. Therefore, trends could be obtained from the decades-old serum data that would be relevant in exploring vitamin D-related hypotheses in future studies.

The purpose of this study was to evaluate the effect of low Ca intake on the 10-year incidence of vertebral fractures in cohorts I and II of the Japan Public Health Centre-based Prospective Study. The baseline studies were conducted in 1990–1994, with the follow-up studies conducted after 10 years. We analysed 33 970 subjects aged 40–59 years in cohort I and 41 664 subjects aged 40–69 years in cohort II. At baseline, the intake of Ca was assessed as a predictor, using validated FFQ. A meta-analysis was performed to estimate a summary relative risk (RR) for the two cohort studies. The 10-year cumulative incidences of self-reported vertebral fractures were 0·38 % for cohort I and 0·56 % for cohort II. In women, lower Ca intake was associated with a higher incidence of vertebral fractures (P for trend = 0·001), with the lowest quartile of Ca intake having a significantly higher incidence (0·89/1000 persons per year or RR 2·10 (95 % CI 1·25, 3·55)) than that (0·42/1000 persons per year) of the highest. In addition, the RR calculated using energy-adjusted Ca intake (by the residual method) as an outcome was 1·92 (95 % CI 1·28, 2·88). However, no such association was observed in men. An increase of Ca intake should be considered as a preventive strategy for vertebral fractures in peri- and post-menopausal women with a low Ca intake.

The present study compared the effects of a high- and normal-casein-protein breakfast on satiety, ‘satiety’ hormones, plasma amino acid responses and subsequent energy intake. Twenty-five healthy subjects (BMI 23·9 (sem 0·3) kg/m2; age 22 (sem 1) years) received a subject-specific standardised breakfast (20 % of daily energy requirements): a custard with casein as the single protein source with either 10, 55 and 35 (normal-casein breakfast) or 25, 55 and 20 (high-casein breakfast) % of energy (En%) from protein, carbohydrate and fat respectively in a randomised, single-blind design. Appetite profile (visual analogue scale; VAS), plasma glucose, insulin, glucagon-like peptide 1, ghrelin and amino acid concentrations were determined for 4 h; here the sensitive moment in time for lunch was determined. Subjects came for a second set of experiments and received the same custards for breakfast, and an ad libitum lunch was offered at 180 min after breakfast; energy intake was assessed. There were increased scores of fullness and satiety after the 25 En% casein-custard compared with the 10 En% casein-custard, particularly at 180 min (26 (sem 4) v. 11 (sem 5) mm VAS; P < 0·01) and 240 min (13 (sem 5) v. − 1 (sem 5) mm VAS; P < 0·01). This coincided with prolonged elevated plasma amino acid concentrations; total amino acids and branched-chain amino acids were higher after the 25 En% casein-custard compared with the 10 En% casein-custard at 180 and 240 min (P < 0·001). There was no difference in energy intake (3080 (sem 229) v. 3133 (sem 226) kJ for 25 En% and 10 En% respectively; NS) from the ad libitum lunch. In conclusion, a breakfast with 25 % of energy from casein is rated as being more satiating than a breakfast with 10 % of energy from casein at 3 and 4 h after breakfast, coinciding with prolonged elevated concentrations of plasma amino acids, but does not reduce subsequent energy intake.