Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

Dietary flaxseed (FS) inhibited the growth of human breast tumours and enhanced the effectiveness of tamoxifen (TAM) in athymic mice with low oestradiol (E2) levels. The present study determined whether the n-3 fatty acid-rich cotyledon fraction of FS (FC), alone or in combination with TAM, has a similar effect and thus can substitute for FS. In a 2 × 2 factorial design, ovariectomised mice with established oestrogen receptor (ER)-positive breast tumours (MCF-7) were treated as follows: groups 1 and 2 were fed the basal diet (BD, control) and FC diet (82 g FC/kg), respectively. Groups 3 and 4 with TAM implants (5 mg) were fed the BD and FC diet, respectively. At 8 weeks post-treatment, mice were euthanised, and tumours were analysed by immunohistochemistry and real-time PCR. BD, FC and FC/TAM groups significantly decreased tumour area, but the TAM group did not. Tumour regression in the FC/TAM group was greater compared to the TAM group. FC lowered cell proliferation but had no effect on apoptosis; the opposite was observed with TAM. FC suppressed mRNA expressions of pS2 and insulin-like growth factor 1 receptor (IGF-1R) and protein expressions of ERα, phosphospecific ERα, human epidermal growth factor receptor 2 (HER2), phosphospecific HER2 (pHER2) and amplified in breast 1 (AIB1), while TAM up-regulated mRNA expressions of Bcl2, progesterone receptor and IGF-1R and protein expression of pHER2, and down-regulated ERβ mRNA. FC modulated the effect of TAM on tumour growth biomarkers. In conclusion, FC reduced the growth of ER+human breast tumours at low circulating E2, alone and combined with TAM, in part through modulation of ER −  and growth factor-mediated signalling pathways; it may substitute for FS in increasing the effectiveness of TAM.

The present study was conducted to evaluate the mechanism by which n-3 PUFA regulates the inhibitor of κBα (IκBα)/NF-κB/muscle RING finger 1 (MuRF1) pathway in C2C12 myotubes. After treatment with 150, 300 or 600 μm-α-linolenic acid (ALA) or -EPA for 24 h in C2C12 myotubes, the levels of phosphorylated IκBα (p-IκBα) and total IκBα were measured by Western blot. Compared with the bovine serum albumin (BSA) control, 150 and 300 μm-ALA and -EPA, respectively, did not affect the total IκBα protein level (P>0·05). However, 600 μm-EPA, but not 600 μm-ALA, prevented IκBα phosphorylation and increased the total IκBα levels (P < 0·01). Furthermore, total nuclear protein was isolated and analysed by the electrophoretic mobility shift assay for NF-κB DNA-binding activity after treatment with 600 μm-ALA or -EPA for 24 h. EPA (600 μm), but not ALA (600 μm), decreased the NF-κB DNA-binding activity when compared with BSA (P < 0·01). It was further observed that 600 μm-EPA caused a 3·38-fold reduction in the levels of MuRF1 mRNA expression compared with BSA (P < 0·01). Additionally, 600 μm-EPA resulted in a 2·3-fold induction of PPARγ mRNA expression (P < 0·01). In C2C12 myotubes, PPARγ knockdown by RNA interference significantly decreased PPARγ mRNA and protein expression to approximately 50 and 60 % (P < 0·01), respectively. Interestingly, in C2C12 myotubes with PPARγ knockdown, 600 μm-ALA and -EPA did not affect the levels of p-IκBα and total IκBα, NF-κB DNA-binding activity or MuRF1 mRNA expression when compared with BSA (P>0·05). These results revealed that EPA, but not ALA, inhibited the IκBα/NF-κB/MuRF1 pathway in C2C12 myotubes in a PPARγ-dependent manner.

Purinergic receptors are important for the regulation of inflammation, muscle contraction, neurotransmission and nociception. Extracellular ATP and its metabolites are the main ligands for these receptors. Occasional reports on beneficial results of ATP administration in human and animal studies have suggested the bioavailability of oral ATP supplements. We investigated whether prolonged daily intake of oral ATP is indeed bioavailable. Thirty-two healthy subjects were randomised to receive 0, 250, 1250 or 5000 mg ATP per d for 28 d by means of enteric-coated pellets. In addition, on days 0 and 28, all thirty-two subjects received 5000 mg ATP to determine whether prolonged administration would induce adaptations in the bioavailability of ATP. ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations. On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study.

The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185 %) and improved clearance (+25 %) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

The effects of wheat and rye breads made from whole-wheat grain (WWG), wheat aleurone flour (WAF) or rye aleurone flour (RAF) on net portal absorption of carbohydrate-derived nutrients (glucose, SCFA and lactate) and apparent insulin secretion were studied in a model experiment with catheterised pigs. The breads were similar in dietary fibre (DF, 120–125 g/kg DM) but differed in arabinoxylans (50–62 g/kg), β-glucans (4–9 g/kg) and content of soluble DF (13–29 g/kg). Six pigs in a repeated 3 × 3 crossover design were fitted with catheters in the portal vein and the mesenteric artery and a portal flow probe. Pigs were fed three meals daily (at 09.00, 14.00 and 19.00 hours), and blood profiles were collected repeatedly from 08.30 until 19.00 hours once weekly. Net portal absorption of glucose was similar among breads and between meals. In contrast, insulin secretion was lowest (P < 0·05) in pigs fed RAF bread (3·9 nmol/h), intermediate in pigs fed WAF bread (5·4 nmol/h) and highest in pigs fed WWG bread (5·9 nmol/h), indicating that RAF bread improved insulin economy. Portal concentrations of propionate, butyrate and valerate were high, intermediate and low (P < 0·05) when pigs were fed RAF, WAF and WWG breads, respectively. Insulin secretion was higher (P < 0·001), and portal absorption of SCFA was lower (P < 0·05) after the first daily meal than after the second daily meal (8·8 v. 4·4 nmol/h). A low insulin response was associated with high portal absorption of SCFA. In conclusion, RAF bread was able to improve insulin economy compared to WWG bread.

Red meat intake is associated with an increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci (ACF), in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion and normalises faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-Ca control diet-fed rats. The present study was designed to find a Ca supplementation with no adverse effect, by testing several doses and types of Ca salts. One in vitro study and two short-term studies in rats identified calcium carbonate as the most effective Ca salt to bind haem in vitro and to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity and thiobarbituric acid-reactive substances. A long-term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 μmol/g calcium carbonate did not promote ACF, in contrast with a previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention.

The present study examined the effects of milk protein on rehydration after exercise in the heat, via the comparison of energy- and electrolyte content-matched carbohydrate and carbohydrate–milk protein solutions. Eight male subjects lost 1·9 (sd 0·2) % of their body mass by intermittent exercise in the heat and rehydrated with 150 % of their body mass loss with either a 65 g/l carbohydrate solution (trial C) or a 40 g/l carbohydrate, 25 g/l milk protein solution (trial CP). Urine samples were collected before and after exercise and for 4 h after rehydration. Total cumulative urine output after rehydration was greater for trial C (1212 (sd 310) ml) than for trial CP (931 (sd 254) ml) (P < 0·05), and total fluid retention over the study was greater after ingestion of drink CP (55 (sd 12) %) than that after ingestion of drink C (43 (sd 15) %) (P < 0·05). At the end of the study period, whole body net fluid balance (P < 0·05) was less negative for trial CP ( − 0·26 (sd 0·27) litres) than for trial C ( − 0·52 (sd 0·30) litres), and although net negative for both the trials, it was only significantly negative after ingestion of drink C (P < 0·05). The results of the present study suggest that when matched for energy density and fat content, as well as for Na and K concentration, and when ingested after exercise-induced dehydration, a carbohydrate–milk protein solution is better retained than a carbohydrate solution. These results suggest that gram-for-gram, milk protein is more effective at augmenting fluid retention than carbohydrate.

The objective of this study was to determine the association between weight loss and drug-induced hepatotoxicity (DIH). A retrospective observational study of 192 active tuberculosis (TB) patients consecutively admitted in a tertiary referral TB centre in the Netherlands was conducted. The outcome measure for DIH was defined as hepatotoxicity necessitating interruption of anti-TB drugs. Multivariate logistic regression analysis on interruption of anti-TB drugs was performed, with age, sex, nutritional status, TB disease severity, drug resistance, comorbidity including baseline liver function tests, anti-TB drug regimen, co-medication and addictions as independent risk factors. Anti-TB drugs were interrupted in thirty-one patients (16·1 %). The most important risk factor was weight loss of 2 kg or more within 4 weeks during TB treatment (OR 211, 95 % CI 36·0, 1232). Other independent risk factors were infection with hepatitis C (OR 19·6, 95 % CI 2·4, 164), age over 60 years (OR 18·5, 95 % CI 2·3, 151) and multi-drug-resistant TB (OR 8·2, 95 % CI 1·3, 53·6). This study shows that weight loss during TB treatment was the most important risk factor for DIH necessitating interruption of anti-TB drugs. Causes of weight loss during TB treatment and the association between weight change and hepatotoxicity need further investigation.

The impact of controlled administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on the risk of acute infectious diseases was studied in healthy newborn infants. In this double-blind, placebo-controlled study, 109 newborn 1-month-old infants were assigned randomly to a probiotic group receiving a BB-12-containing tablet (n 55) or to a control group receiving a control tablet (n 54). Test tablets were administered to the infants twice a day (daily dose of BB-12 10 billion colony-forming units) from the age of 1–2 months to 8 months with a novel slow-release pacifier or a spoon. Breastfeeding habits, pacifier use, dietary habits, medications and all signs and symptoms of acute infections were registered. At the age of 8 months, faecal samples were collected for BB-12 determination (quantitative PCR method). The baseline characteristics of the two groups were similar, as was the duration of exclusive breastfeeding. BB-12 was recovered (detection limit log 5) in the faeces of 62 % of the infants receiving the BB-12 tablet. The daily duration of pacifier sucking was not associated with the occurrence of acute otitis media. No significant differences between the groups were observed in reported gastrointestinal symptoms, otitis media or use of antibiotics. However, the infants receiving BB-12 were reported to have experienced fewer respiratory infections (65 v. 94 %; risk ratio 0·69; 95 % CI 0·53, 0·89; P = 0·014) than the control infants. Controlled administration of BB-12 in early childhood may reduce respiratory infections.

Recently, novel dietary oils with modified fatty acid profiles have been manufactured to improve fatty acid intakes and reduce CVD risk. Our objective was to evaluate the efficacy of novel high-oleic rapeseed (canola) oil (HOCO), alone or blended with flaxseed oil (FXCO), on circulating lipids and inflammatory biomarkers v. a typical Western diet (WD). Using a randomised, controlled, crossover trial, thirty-six hypercholesterolaemic subjects consumed three isoenergetic diets for 28 d each containing approximately 36 % energy from fat, of which 70 % was provided by HOCO, FXCO or WD. Dietary fat content of SFA, MUFA, PUFA n-6 and n-3 was 6, 23, 5, 1 % energy for HOCO; 6, 16, 5, 7·5 % energy for FXCO; 11·5, 16, 6, 0·5 % energy for WD. After 28 d, compared with WD, LDL-cholesterol was reduced 15·1 % (P < 0·001) with FXCO and 7·4 % (P < 0·001) with HOCO. Total cholesterol (TC) was reduced 11 % (P < 0·001) with FXCO and 3·5 % (P = 0·002) with HOCO compared with WD. Endpoint TC differed between FXCO and HOCO (P < 0·05). FXCO consumption reduced HDL-cholesterol by 8·5 % (P < 0·001) and LDL:HDL ratio by 7·5 % (P = 0·008) v. WD. FXCO significantly decreased E-selectin concentration compared with WD (P = 0·02). No differences were observed in inflammatory markers after the consumption of HOCO compared with WD. In conclusion, consumption of novel HOCO alone or when blended with flaxseed oil is cardioprotective through lipid-lowering effects. The incorporation of flaxseed oil may also target inflammation by reducing plasma E-selectin.

Adequate dietary habits are supposed to be one of the most important modifiable factors in osteoporosis prevention. However, the importance of specific nutrients is controversial. We examined relevant nutrients which are supposed to have an impact on bone parameters and compared their effect sizes with those of two known predictors of bone development: bone-related muscle mass and androgen levels. We analysed nutritional, hormonal and anthropometric data from 107 prepubertal children participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Diaphyseal bone mineral content (BMC), cortical area (CA), periosteal circumference, strength strain index and muscle area of the non-dominant forearm were measured by peripheral quantitative computed tomography. Data on long-term nutrient intakes (e.g. protein, Ca and vitamin D) were derived from 3 d weighed dietary records. Twenty-four hour urinary excretion rates of androgen metabolites including the sex steroid androstenediol were measured using GC–MS. Of all considered nutrients, only protein showed a trend for an association with BMC (β = +0·11; P = 0·073) and CA (β = +0·11; P = 0·056) in stepwise linear regression models. None of the other considered dietary variables was associated with bone parameters. The size of the bone anabolic effect of protein was partly comparable with that of androstenediol. Even though boys gained more bone mass in comparison with girls, the protein effect did not differ between sexes. Bone-related muscle area and sex steroids have the strongest effects on prepubertal diaphyseal bone. However, dietary protein may have a similar bone anabolic influence compared with androstenediol. In children without explicit nutrient deficits, protein seems to be the most important dietary component for diaphyseal bone status.

Few multi-ethnic national surveys have examined Zn nutriture, despite its importance for optimal growth and development during childhood. We assessed the Zn status of urban and semi-urban children aged 5–15 years from three ethnic groups in New Zealand (NZ) in the 2002 Children's National Nutrition Survey and investigated the factors predisposing them to Zn deficiency. In a 10-month cross-sectional survey, Pacific and Māori children were over-sampled permitting ethnic-specific analyses. Anthropometry, serum Zn and Zn intakes via 24 h recalls were measured. Anthropometric z scores were highest in Pacific children. Overall, mean adjusted serum Zn at 11 years was for males and females, respectively: 11·9 (95 % CI 11·5, 12·3) and 12·5 (95 % CI 12·0, 12·9) μmol/l in NZ European and Other (NZEO) children (n 395); 11·9 (95 % CI 11·4, 12·4) and 12·0 (95 % CI 11·4, 12·5) μmol/l in Māori children (n 379); and 11·5 (95 % CI 11·1, 11·9) and 11·4 (95 % CI 11·1, 11·8) μmol/l in Pacific children (n 589). The predictors of serum Zn were age, serum Se and sex for NZEO children; serum Se and age for Pacific children; and none for Māori children. Pacific children had the highest prevalence of low serum Zn (21 (95 % CI 11, 30) %), followed by Māori children (16 (95 % CI 12, 20) %) and NZEO children (15 (95 % CI 9, 21) %). Prevalence of inadequate Zn intakes, although low, reached 8 % for Pacific children who had the lowest Zn intake/kg body weight. Pacific boys but not girls with low serum Zn had a lower mean height-for-age z-score (P < 0·007) than those with normal serum Zn. We conclude that the biochemical risk of Zn deficiency in Pacific children indicates a public health problem. However, a lack of concordance with the risk of dietary Zn inadequacy suggests the need for better defined cut-offs in children.

The use of two non-consecutive 24 h recalls using EPIC-Soft for standardised dietary monitoring in European countries has previously been proposed in the European Food Consumption Survey Method consortium. Whether this methodology is sufficiently valid to assess nutrient intake in a comparable way, among populations with different food patterns in Europe, is the subject of study in the European Food Consumption Validation consortium. The objective of the study was to compare the validity of usual protein and K intake estimated from two non-consecutive standardised 24 h recalls using EPIC-Soft between five selected centres in Europe. A total of 600 adults, aged 45–65 years, were recruited in Belgium, the Czech Republic, France, The Netherlands and Norway. From each participant, two 24 h recalls and two 24 h urines were collected. The mean and distribution of usual protein and K intake, as well as the ranking of intake, were compared with protein and K excretions within and between centres. Underestimation of protein (range 2–13 %) and K (range 4–17 %) intake was seen in all centres, except in the Czech Republic. We found a fair agreement between prevalences estimated based on the intake and excretion data at the lower end of the usual intake distribution ( < 10 % difference), but larger differences at other points. Protein and K intake was moderately correlated with excretion within the centres (ranges = 0·39–0·67 and 0·37–0·69, respectively). These were comparable across centres. In conclusion, two standardised 24 h recalls (EPIC-Soft) appear to be sufficiently valid for assessing and comparing the mean and distribution of protein and K intake across five centres in Europe as well as for ranking individuals.

Diet plausibly has a role in the aetiology of endometriosis through effects on steroid hormone levels; however, few published studies have examined the diet and endometriosis risk. We evaluated dietary risk factors for endometriosis in a population-based case–control study. Cases were 284 Group Health (GH) enrollees aged 18–49 years with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001. Controls were 660 randomly selected age-matched female GH enrollees without a history of endometriosis. Nutrients and selected food groups were assessed using the Women's Health Initiative FFQ. OR of endometriosis risk associated with dietary exposures were estimated using unconditional logistic regression and adjusted for identified covariates. Increased total fat consumption was associated with decreased endometriosis risk (fourth quartile v. lowest: OR 0·5, 95 % CI 0·2, 1·0, P-trend = 0·12). Increased β-carotene consumption and servings/d of fruit were associated with increased risk (β-carotene third quartile v. lowest: OR 1·7, 95 % CI 1·1, 2·6; fourth quartile v. lowest: OR 1·6, 95 % CI 1·0, 2·5, P-trend 0·16; fruit >2 servings/d v. < 1: OR 1·5, 95 % CI 1·0, 2·3, P-trend = 0·04). We also found a suggestion of decreased endometriosis risk associated with the consumption of dairy products (2 servings/d v. ≤ 1: OR 0·6, >2 servings/d v. ≤ 1: OR 0·7), but this association was not statistically significant for the highest tertile. The present study suggests that specific dietary components may be associated with endometriosis risk.

The average reported dietary Na intake of children in Australia is high: 2694 mg/d (9–13 years). No data exist describing food sources of Na in Australian children's diets and potential impact of Na reduction targets for processed foods. The aim of the present study was to determine sources of dietary Na in a nationally representative sample of Australian children aged 2–16 years and to assess the impact of application of the UK Food Standards Agency (FSA) Na reduction targets on Na intake. Na intake and use of discretionary salt (note: conversion of salt to Na, 1 g of NaCl (salt) = 390 mg Na) were assessed from 24-h dietary recall in 4487 children participating in the Australian 2007 Children's Nutrition and Physical Activity Survey. Greatest contributors to Na intake across all ages were cereals and cereal-based products/dishes (43 %), including bread (13 %) and breakfast cereals (4 %). Other moderate sources were meat, poultry products (16 %), including processed meats (8 %) and sausages (3 %); milk products/dishes (11 %) and savoury sauces and condiments (7 %). Between 37 and 42 % reported that the person who prepares their meal adds salt when cooking and between 11 and 39 % added salt at the table. Those over the age of 9 years were more likely to report adding salt at the table (χ2 199·5, df 6, P < 0·001). Attainment of the UK FSA Na reduction targets, within the present food supply, would result in a 20 % reduction in daily Na intake in children aged 2–16 years. Incremental reductions of this magnitude over a period of years could significantly reduce the Na intake of this group and further reductions could be achieved by reducing discretionary salt use.

The use of skinfold thickness measurements to evaluate the distribution of subcutaneous adipose tissue and to predict body fat has recognised advantages. However, the different types of skinfold calliper available present limitations that make them unattractive and perhaps less used in daily practice. The purpose of the present study was to evaluate the accuracy and functionality of a new digital skinfold system, the Liposoft 2008+Adipsmeter V0 (LA), for measuring skinfold thickness and determining body fat proportion (%BF). Skinfold thickness measurements made by the LA were compared with those obtained with a Harpenden (H) calliper from two samples of adults (n 45) and older adults (n 56) in a university-based cross-sectional study. A comparison was also conducted between estimated %BF from skinfolds and dual-energy X-ray absorptiometry. Bland and Altman plots show that skinfolds measured by the LA and H calliper are in high agreement, with a mean difference of 0·3 (95 % CI − 3·1, 3·4) mm. In regard to the %BF estimated from LA and H skinfolds measurement, the LA produced a similar approximation to dual-energy X-ray absorptiometry %BF, with a mean difference of 0·2 (95 % CI − 0·8, 1·2) %, compared with %BF obtained with the H calliper. The LA system is an accurate instrumentation and represents an innovation in the evaluation of skinfold thickness and body composition based on anthropometric measurement.