ALBERT

Description: Purpose Maintenance of cognitive abilities is important for elderly to stay independent. With the aging of the population, the call for modifiable factors is emerging. Dietary protein might improve cognitive performance; however, this has hardly been studied. Therefore, we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people. Methods Pre-frail and frail elderly subjects, according to the Fried criteria, randomly received a protein drink containing 15 g protein or a placebo drink twice a day. Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery. In addition, reaction time was assessed after both 12 and 24 weeks of intervention. Domain scores were calculated for the domains episodic memory, attention and working memory, information processing speed, and executive functioning. Analyses of covariance were used to determine differences between groups. Linear mixed models were used to determine differences in reaction time over time and per treatment. Results In total, 65 subjects (79 ± 8 years) with a median Mini-Mental State Examination score of 28 (interquartile range 26–30) were included. Reaction time improved more in the protein group (68 ms) than in the placebo group (18 ms, P  = 0.03). Dietary protein had no significant effect on any of the cognitive domain scores. Conclusions Protein supplementation might improve reaction time performance in pre-frail and frail elderly, but did not improve other cognitive functions.

Description: Purpose Up-to-date knowledge about vitamin D supply and serum concentration in Germany is not sufficient. Our purpose was to compare a novel holistic bottom-up modeling of 25(OH)D concentrations with vitamin D sources such as sunlight, food and supplements for all federal states taking seasonal and geographical variations into account. The second purpose was to update and detail vitamin D supply through food in Germany. Methods To confirm the model of 25(OH)D concentrations, we used the population (1,763 men and 2,267 women, 18–79 years) participated in the representative German National Health Interview and Examination Survey 1998 and the integrated German Nutrition Survey. Results The maximum model value is 67.5 nmol/L in July and minimum model value is 29.3 nmol/L in January, while the average model value is 45.0 nmol/L. Men have a mean daily intake of 137 IU (3.42 μg) and women of 112 IU (2.79 μg). Correlation between model and actual data is 0.77 ( p  = 0.003). Conclusions A comparison of the model data with population-based values showed good agreement. None of the vitamin D sources can provide the German population with enough vitamin D.

Description: Purpose Some researchers found decreased levels of plasma taurine in obese subjects and animals, and reduced expression of an important enzyme of taurine synthesis. These evidences, coupled with the metabolic imbalance of obesity and the possible anti-inflammatory and antioxidant effects of taurine, highlighted the use of taurine as a supplement in obesity treatment. The aim of the present study was to investigate whether taurine supplementation, associated with nutritional counseling, modulates oxidative stress, inflammatory response, and glucose homeostasis in obese women. Methods A randomized double-blind placebo-controlled study was conducted with 16 women with obesity diagnosis and 8 women in the normal weight range. The obese volunteers were matched by age and body mass index and randomly assigned to either the placebo (3 g/day starch flour) or taurine (3 g/day taurine) group. The study lasted 8 weeks, and the experimental protocol included nutritional assessment and determination of plasma sulfur amino acids, insulin, and adiponectin, serum glycemia, and markers of inflammatory response and oxidative stress. Results Plasma taurine levels were significantly decreased (41 %) in the obese volunteers. Both the placebo and taurine groups showed significant reduction in weight (3 %), with no differences between groups. Different from placebo, taurine-supplemented group showed significant increase in plasma taurine (97 %) and adiponectin (12 %) and significant reduction in the inflammatory marker hs-C-reactive protein (29 %) and in the lipid peroxidation marker thiobarbituric acid reactive substances (TBARS) (20 %). Conclusions Eight weeks of taurine supplementation associated with nutritional counseling is able to increase adiponectin levels and to decrease markers of inflammation (high-sensitivity C-reactive protein) and lipid peroxidation (TBARS) in obese women.

Description: Purpose Even mild iodine deficiency may negatively affect cognitive performance, especially at a young age. Our aim was to investigate iodine status in very young children and to assess the importance of iodized salt in processed foods of which the use has decreased during the last years in Germany. Methods Twenty-four hours urinary iodine excretion (UIE) as a marker of iodine intake was measured in 378 24 h urine samples collected 2003–2010 by 221 3 to 〈6 years old participants of the DONALD Study. Parallel 3-d weighed dietary records and measurements of urinary sodium excretion provided data on the daily consumption of the most important iodine sources in the children’s diet (iodized salt, milk, fish, meat and eggs). Time trends of UIE (2003–2010) and contributions of the different food groups were analyzed by using linear mixed-effects regression models. Results Median UIE of 71 μg/d in boys and 65 μg/d in girls ( P  = 0.03), corresponding to an iodine intake of 82 and 75 μg/d, respectively (assumption: 15 % non-renal iodine losses), was below the recommended dietary allowance (RDA) of 90 μg/d. Milk, salt and egg intake were significant predictors of UIE; milk and salt together accounted for 〉80 % of iodine supply. Between 2003 and 2010, UIE decreased significantly by approximately 1 μg/d per year. The contribution of salt intake to UIE decreased from 2003–2006 to 2007–2010. Conclusion In countries where salt is a major iodine source, already modest decreases in the iodized proportion of salt used in processed foods may relevantly impair iodine status even in preschool children.

Description: Purpose Urolithins, gut microbiota metabolites derived from ellagic acid and ellagitannins, reach micromolar concentrations in the colon lumen where can have anti-inflammatory and anticancer effects. The antiproliferative activity of urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480 and HT-29). Methods Cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays. Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC–MS/MS. Results Urolithins inhibited cell proliferation and cell cycle progression in a time- and dose-dependent manner and arrested the cells at S and G2/M phases, depending on the urolithin. Uro-A exerted the highest antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was related to the complete glucuronidation of urolithins. Uro-A or Uro-B glucuronides did not affect cell cycle and showed lower antiproliferative activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug efflux ABC transporters partially prevented the glucuronidation of urolithins in HT-29 cells which became more sensitive. Conclusions Uro-A, Uro-B, Uro-C and Uro-D exerted different antiproliferative effects depending on the colon cancer cell line. We also report here, for the first time, the role of ABC transporters and Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against urolithins due to their conversion to glucuronide conjugates that exerted lower antiproliferative activity.

Description: Purpose The primary objective of this study is to investigate the content of biologically active compounds producing an antioxidant effect in Plantago maxima and their influence on main mechanisms of dietary obesity development. Methods Biologically active compounds in P. maxima were tested using paper chromatography. In in vivo experiment, high-fat-fed Wistar rats obtained P. maxima water extract for 3 months. Morphometric parameters, weight gain, serum adipokines, and cytokines, as well as oxidative stress biomarkers in rats’ tissues were evaluated. Gut microflora was also examined. Results Plantago maxima leaves used in the experiment contained significant amount of flavonoids, iridoids, phenol carboxylic acids, and tannins and ascorbic acid. Our in vivo experiment data demonstrate that P. maxima water extract prevents excessive adiposity in a diet-induced model. P. maxima consumption reduced serum leptin (twofold), macrophage chemoattractant protein-1 (sevenfold), tumor-necrosis factor-α (25 %), and interleukine-6 (26 %) levels. P. maxima water extract decreased adipose tissue oxidative stress biomarkers in rats fed a high-fat diet. In addition, increased bacterial growth in the diet-induced obesity model was reversed by the P. maxima extract treatment. Conclusion Plantago maxima water extract possessed antiadipogenic, antidiabetic, antiinflammatory, antioxidant activity, and normalized gut microflora in a rat model of diet-induced excessive adiposity due to a high content of biologically active compounds.

Description: Purpose d , l -Sulforaphane (SFN) is a promising chemopreventive agent with in vivo efficacy against prostate cancer in experimental rodents. This study was undertaken to determine the role of vimentin and plasminogen activator inhibitor-1 (PAI-1) in anticancer effects of SFN. Methods Effect of SFN on levels of different proteins was determined by Western blotting or immunofluorescence microscopy. RNA interference of vimentin and PAI-1 was achieved by transient transfection. Apoptosis was quantified by flow cytometry. Transwell chambers were used to determine cell migration. Results Exposure of PC-3 and DU145 human prostate cancer cells to SFN resulted in induction of vimentin protein, which was accompanied by down-regulation of E-cadherin protein expression. The SFN-mediated induction of vimentin was also observed in a normal human prostate epithelial cell line. RNA interference of vimentin did not have any appreciable effect on early or late apoptosis resulting from SFN exposure. On the other hand, SFN-mediated inhibition of PC-3 and DU145 cell migration was significantly augmented by knockdown of the vimentin protein. Knockdown of vimentin itself was inhibitory against cell migration. The SFN-treated cells also exhibited induction of PAI-1, which is an endogenous inhibitor of urokinase-type plasminogen activator system. Similar to vimentin, PAI-1 knockdown resulted in a modest augmentation of PC-3 cell migration inhibition by SFN. Tumors from SFN-treated transgenic adenocarcinoma of mouse prostate mice showed a 1.7-fold increase in vimentin protein level compared with control tumors. Conclusion The present study indicates that vimentin and PAI-1 inductions confer modest protection against SFN-mediated inhibition of prostate cancer cell migration.

Description: Purpose Since obesity is associated with poorer iron status, the effects of diet-induced obesity on iron status and iron-regulatory pathways were examined. Methods Weanling male diet-induced obese sensitive ( n  = 12/diet group) and resistant ( n  = 12/diet group) rats were fed one of four high-fat, high-energy diets supplemented with 5 (5Fe, low), 15 (15Fe, marginal), 35 (35Fe, normal) or 70 (70Fe, high) mg iron/kg diet for 12 weeks. At the end of the study, rats in each diet group were categorised as obese (〉19 %) or lean (〈17 %) based on percentage body fat. Results Obese rats gained more weight, had larger total lean mass, consumed more food and showed greater feed efficiency compared with lean rats. Obese rats fed the 5Fe and 15Fe diets had poorer iron status than lean rats fed the same diet. Obese 5Fe rats had lower serum iron and more severe iron-deficiency anaemia. Obese 15Fe rats had lower mean corpuscular haemoglobin and liver iron concentrations. Hepcidin mRNA expression in liver and adipose tissue was similar for obese and lean rats. Iron concentration and content of the iron transporters divalent metal transporter 1 and ferroportin 1 in duodenal mucosa were also similar. Conclusions Obese rats that were larger, regardless of adiposity, had higher iron requirements compared with lean rats that appeared independent of hepcidin, inflammation and intestinal iron absorption. Higher iron requirements may have resulted from larger accretion of body mass and blood volume. Greater food consumption did not compensate for the higher iron needs, indicating increased susceptibility to iron deficiency.

Description: Introduction Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2 μM) in association with Vc (100 μM) on functional parameters of human neutrophils in vitro. Materials and methods We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O 2 ·− , H 2 O 2 , HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli. Results We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio. Conclusion In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils.

Description: Purpose The aim of this study was to investigate the associations between proxy-reported energy intake, daily food intake and energy density of foods and body mass index (BMI) z -score in 2–9-year-old European children. Methods From 16,225 children who participated in the identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) baseline examination, 9,782 children with 24-h proxy dietary information and complete covariate information were included in the analysis. Participating children were classified according to adapted Goldberg cutoffs: underreports, plausible energy reports and overreports. Energy intake, daily food intake and energy density of foods excluding noncaloric beverages were calculated for all eating occasions. Effect of energy intake, daily food intake and energy density of foods on BMI z -score was investigated using multilevel regression models in the full sample and subsample of plausible energy reports. Exposure variables were included separately; daily food intake and energy intake were addressed in a combined model to check for interactions. Results In the group of plausible energy reports ( N  = 8,544), energy intake and daily food intake were significantly positively associated with BMI z -score. Energy density of foods was not associated with BMI z -score. In the model including energy intake, food intake and an interaction term, only energy intake showed a significantly positive effect on BMI z -score. In the full sample ( N  = 9,782), only energy intake was significantly but negatively associated with BMI z -score. Conclusion Proxy-reporters are subject to misreporting, especially for children in the higher BMI levels. Energy intake is a more important predictor of unhealthy weight development in children than daily food intake.

Description: Purpose A low calcium intake (LCaI) may predispose to obesity, and excessive fat mass may be detrimental to bone. The impact of Ca inadequacy would be greater in subjects predisposed to obesity. LCaI effect on obesity development during the rapid growth period was compared in two strains of rats: spontaneously obese IIMb/β (O) and Wistar (W). Pregnant rats were fed 0.5 % (N) or 0.2 % (L) of Ca (OLCa, ONCa, WLCa and WNCa). Male pups were fed the maternal diet until day 60. Methods Body composition, lipid profile, glucose homeostasis, 25 hydroxyvitamin D, Ca-phosphorus, and bone metabolism were evaluated. Results BW and body fat were higher, whereas body protein was lower in OLCa versus ONCa ( p  〈 0.05). OLCa presented the highest body fat, glucose, non-HDL and total cholesterol, TGL, insulin levels, and HOMA-IR, liver weight, and adipose perigonadal plus retroperitoneal pads ( p  〈 0.05). WLCa did not exhibit an increase BW and only showed a slight change in body composition with minor biochemical alterations compared to WNCa ( p  〈 0.05). Osteocalcin, CTX, and proximal tibia and lumbar spine BMDs were lower in O than in W rats fed the same Ca diet ( p  〈 0.05). Body ash and Ca content, and total skeleton BMC/BW were lower in OLCa and WLCa versus their corresponding NCa groups ( p  〈 0.05). Conclusion The negative effect of a low Ca diet on fat mass accumulation and lipid profile may be more evident in rats predisposed to obesity. Nevertheless, low CaI interferes with the normal glucose homeostasis leading to an increase in insulin resistance. Low CaI during early growth may be an obesogenic factor that may persist into adult life and may account for the development of obesity and some of its co-morbidities.

Description: Purpose The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance. Methods This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6 % β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control. Results The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation. Conclusion These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.

Description: Purpose Rats given sugar-sweetened drinks can develop glucose intolerance, insulin resistance and dyslipidaemia. The aim of this study was to investigate whether such metabolic disruptions and also possible weight gain induced by chronic sucrose consumption could be attenuated by low-volume exercise. Methods Using a 2 × 2 factorial design, rats were given free access for 57 days to either a 10 % sucrose solution ( Suc and SucEx ) or water only ( Con and ConEx ), while exercise rats ( SucEx and ConEx ) received 20-min treadmill training every 3 days. Caloric intake and body weight were measured throughout this dietary intervention. Oral glucose tolerance tests were performed on days 29 and 54. Plasma insulin, triglycerides and leptin were also measured, together with post-mortem measures of retroperitoneal fat pads and liver triglycerides. Results In groups given sucrose, exercise reduced calorie consumption, reduced weight gain and decreased leptin relative to non-exercised controls. Exercise was found to improve glucose tolerance and insulin action at day 29, but not day 54. Conclusions Low-volume exercise can be effective in preventing weight gain in sucrose-fed rats, probably via reduction of subcutaneous fat, but prevention of the glucose intolerance and dyslipidaemia produced by sucrose consumption may be transient.

Description: Purpose Laboratory studies have suggested that vitamin D inadequacy may be implicated in development of hypertension. Evidence from epidemiologic studies remains limited. We aim to examine the prospective associations of circulating vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their interaction with risk of hypertension. Methods We conducted prospective analyses among 1,211 US men that were free of baseline hypertension and had baseline plasma 25hydroxy-vitamin D (25(OH)D) or 1,25dihydroxy-vitamin D (1,25(OH) 2 D) measured and VDR Bsm I or Fok I polymorphisms genotyped. Results During 15.3-year follow-up, 695 men developed incident hypertension. After multivariable adjustment, the hazard ratios (HRs) and 95 % CIs for hypertension across increasing quartiles of plasma vitamin D metabolites were 1.00 (ref), 0.94 (0.69–1.27), 0.69 (0.50–0.96), and 0.82 (0.60–1.13) for 25(OH)D ( p , trend: 0.43), and 1.00, 0.92 (0.66–1.27), 1.12 (0.82–1.54), and 1.19 (0.86–1.63) for 1,25(OH) 2 D ( p , trend: 0.16). Compared with carriers of VDR Bsm I bb, carriers of bB or BB had a HR of 1.25 (1.04–1.51) for hypertension. For VDR Fok I polymorphism, compared with carriers of FF and Ff combined, carriers of ff had a HR of 1.32 (1.03–1.70). The relation between plasma 25(OH)D and risk of hypertension did not differ by VDR Bsm I and Fok I polymorphisms. Conclusions In a prospective cohort of men, we found suggestive evidence for an inverse association between plasma 25(OH)D and risk of hypertension. We also found associations between VDR Bsm I and Fok I polymorphisms with hypertension risk. More research is needed to further determine the role of vitamin D in hypertension prevention.

Description: Purpose The dietary sesamol is one of the important constituent of sesame seed that has been mainly claimed to combat cardiovascular disease and diabetes, which are the major secondary complications of arthritis. Thus, the present study was designed to evaluate the anti-arthritic, anti-inflammatory and anti-stress potentials of sesamol. Methods Arthritis was induced using Freund’s complete adjuvant to hind paw of experimental rats. The physical and biochemical alterations and its recovery by sesamol were assessed by measuring enzymatic and non-enzymatic mediators. Arthritis-induced inflammation, oxidative stress and their protective by sesamol were measured by determining the levels of pro-inflammatory cytokines and oxidative stress markers. Results In the present study, sesamol was demonstrated to alleviate arthritis-induced cartilage degeneration by mitigating augmented serum levels of hyaluronidase and matrix metalloproteinases (MMP-13, MMP-3 and MMP-9). It also protected bone resorption by reducing the elevated levels of bone joint exoglycosidases, cathepsin D and tartarate-resistant acid phosphatases. Sesamol also abrogated the non-enzymatic inflammatory markers (TNF, IL-1β, IL-6, COX-2, PGE 2 , ROS, and H 2 O 2 ,) effectively. In addition, sesamol neutralizes arthritis-induced oxidative stress by restoring the levels of reactive oxygen species, lipid and hydro peroxides and sustained antioxidant homeostasis by re-establishing altered activities of superoxide dismutase, catalase and glutathione-s-transferase. Conclusion Taken together, the study demonstrated the anti-arthritic, anti-inflammatory, anti-oxidative stress and chondro-protective potentials of sesamol in vivo. Thus, sesamol could be a single bullet that can fight arthritis as well as the secondary complications of arthritis such as cardio vascular disorders and diabetes.

Description: Purpose We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect. Methods Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks. Results C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % ( P  〈 0.001) lower plasma cholesterol, 40 ± 5 % ( P  〈 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae , Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl. Conclusions Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.

Description: Background/objectives Individuals with type 1 diabetes have a high risk of developing cardiovascular diseases, and it has been reported that they consume a high atherogenic diet. We examined how nutrient intake and adherence to current European nutritional recommendations evolved in a large cohort of European individuals with type 1 diabetes over a period of 7 years. Subjects/methods We analysed data from the EURODIAB Prospective Complications Study, a European multicentre prospective cohort study. Standardized 3-day dietary records were employed in individuals with type 1 diabetes. One thousand one hundred and two patients (553 men, 549 women, baseline age 33 ± 10 years, duration 15 ± 9 years) had complete nutritional data available at baseline and after 7 years. We calculated mean differences in reported nutrients over time and adjusted these for age, gender, HbA 1c and BMI with ANOVA models. Results Compared to baseline, there were minor changes in nutrients. Reported protein (−0.35 % energy (en), fat (−1.07 % en), saturated fat (−0.25 % en) and cholesterol (−7.42 mg/1000 kcal) intakes were lower, whereas carbohydrate (+1.23 % en) and fibre (+0.46 g/1000 kcal) intakes were higher at the 7-year follow-up. European recommendations for adequate nutrient intakes were followed in individuals with type 1 diabetes for protein (76 % at baseline and 78 % at follow-up), moderately for fat (34, 40 %), carbohydrate (34, 41 %) and cholesterol (39, 47 %), but poorly for fibre (1.4, 2.4 %) and saturated fat (11, 13 %). Conclusion European individuals with type 1 diabetes consume a high atherogenic diet as few patients met recommendations for dietary fibre and saturated fat. This study showed minor changes in dietary nutrients and energy intakes over a period of 7 years. Nutrition education needs particular focus on strategies to increase dietary fibre and reduce saturated fat to exploit their potential benefit.

Description: Purpose Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups. Methods Subjects were divided into two age groups—32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting. Results Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression. Conclusions TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

Description: Purpose Preterm infants are at risk for suboptimal bone mineralization. Postnatal bone formation requires optimal nutritional composition. This study evaluated the effect of isocaloric, protein-, and mineral-enriched postdischarge formula (PDF), standard term formula (TF), and human milk (HM) on gain in bone mineral content (BMC) of preterm infants between term age (40 weeks postmenstrual age) and 6 months corrected age (CA). Methods Between term age and 6 months CA, 93 preterm infants were randomized to be fed PDF ( n  = 52) or TF ( n  = 41) and 46 preterm infants were fed HM. Weight (g) and length (cm) were measured at birth, term age, and 6 months CA. BMC (g) was measured by whole-body dual-energy x-ray absorptiometry at term age and 6 months CA. Results Gain in BMC (expressed as median with interquartile range) between term age and 6 months CA was higher in PDF-fed infants (102.3 (32.4) g) compared to TF- and HM-fed infants (91.6 (24.5) and 84.5 (33.3) g, respectively), adjusted for gender, gestational age, birthweight, and gain in weight and length. Conclusion Between term age and 6 months CA, isocaloric PDF enhances gain in BMC of preterm infants, independent of gain in weight and length. We speculate that higher gain in BMC during infancy may improve adult bone mass in preterm infants.

Description: Purpose To further inform the debate on the possible cognitive benefits of antioxidant nutrients in the elderly, we systematically reviewed available prospective studies while paying a special attention to their methodological quality. Methods This is a systematic review of studies involving major antioxidant nutrients and change in cognitive performance. Abstracts were independently reviewed; studies were selected based on prespecified criteria. Methodological quality of primary studies was assessed using a methodological checklist for cohort studies. Findings were presented using a narrative synthesis and tabulation of results. Results Eight-hundred and fifty potentially eligible studies were identified; 10 met the inclusion criteria and were retained for data extraction and appraisal. The main supportive evidence came from two studies, both judged to be of high quality: The first observed an accelerated decline in global cognition, attention, and psychomotor speed over 9 years, concomitant to a decrease in plasma selenium levels over the same period; the second study reported a slower rate of global cognitive decline over 3 years in persons in the highest quartile of intake of vitamins C, E, and carotenes. All associations persisted after adjustment for confounding factors. Evidence in favor of beneficial associations of higher dietary intake of vitamin E and flavonoids, as well as higher serum beta carotene levels, came from further studies of only adequate quality. Conclusions There is a possibility for protective effects of antioxidant nutrients against decline in cognition in older people although the supportive evidence is still limited in number. This association deserves further examination in additional quality investigations.

Description: Background and aim Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. Methods After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, β-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. β-Catenin localization was observed by confocal microscopy. Results We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering β-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. Conclusions These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.

Description: Purpose Adipose tissue-associated chronic inflammation is involved in the pathogenesis of obesity-related diseases. Dietary fatty acids are known to influence inflammatory processes. The aim of this study was to investigate, whether diets with regular fat contents but variable fat qualities affect adipose tissue-associated inflammation through the fatty acid composition of mesenteric adipose tissue (MAT). Methods Obese Zucker rats were fed diets containing 7 % wt:wt rapeseed oil, corn oil, or lard for 10 weeks. Fatty acid composition and endocrine function regarding adipokines and cytokines of MAT, number of total CD3 + T cells, and cytokine secretion of mesenteric lymph node (MLN)-derived lymphocytes were determined. Local effects in MAT and MLN were compared to systemic effects assessed in serum and peripheral blood mononuclear cells. Results Fatty acid composition of MAT reflected dietary fatty acid intake, without affecting endocrine function. Feeding the lard diet for 10 weeks increased the serum adiponectin and TNF-α secretion of blood lymphocytes, whereas CD3 + T cells in blood were decreased. No effects were seen for the secretion of adipokines and cytokines from MAT, the amount of T cells in MLN, and cytokine secretion of MLN lymphocytes. Conclusions In conclusion, feeding obese rats a diet with regular fat content but variable fat sources for 10 weeks, changed the fatty acid composition of MAT but not its secretory properties or MLN functions. Although the local immune system was not influenced, lard-feeding induced minor changes in systemic immune function.

Description: Purpose Dietary food composition influences postprandial glucose homeostasis. Thus, the objective was to investigate the effects of an acute intake of three different types of strawberry jam, differing in carbohydrate and antioxidants content, on postprandial glucose metabolism, lipid profile, antioxidant status, and satiety. Methods Sixteen healthy adults participated in a randomized, crossover, double-blind study with three arms, receiving 60 g of three different strawberry jams. Blood samples were collected at fasting and at 30, 60, 90, and 120 min after its intake. Blood analyses were performed with validated procedures and satiety was estimated with visual analogue scale (VAS). Results Blood glucose concentrations were maintained at normal values and without peaks within the 2 h after consumption of low-sugar jams. However, blood glucose and insulin were significantly higher at 30 and 60 min after high-sugar (HS) jam intake versus both low-sugar jams. Furthermore, HS jam produced more satisfaction at short time, but decreased as soon as blood glucose concentration began to decrease. Moreover, HS ingestion produced lower free fatty acid levels ( p  〈 0.05) throughout the trial with respect both the low-sugar jams. However, no additional benefits on oxidative status (malondialdehyde, glutathione peroxidase, total antioxidant capacity, and uric acid), glucose, lipid, and satiety variables were observed due to the inclusion of an antioxidant to low-sugar jam. Conclusions This study reinforces the idea that products without added sugars are appropriate for the management of glycemic alterations and provides further insight into the effect of natural antioxidants as a functional ingredient on oxidative status and related metabolic disturbances. Registered at www.clinicaltrials.gov as NCT01684332.

Description: Purpose Soy isoflavones may inhibit tumor cell invasion and metastasis via their effects on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The current study investigates the effects of daidzein, R- and S-equol on the invasion of MDA-MB-231 human breast cancer cells and the effects of these compounds on MMP/TIMP expression at the mRNA level. Methods The anti-invasive effects of daidzein, R- and S-equol (0, 2.5, 10, 50 μM) on MDA-MB-231 cells were determined using the Matrigel invasion assay following 48-h exposure. Effects on MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were assessed using real-time PCR. Chiral HPLC analysis was used to determine intracellular concentrations of R- and S-equol. Results The invasive capacity of MDA-MB-231 cells was significantly reduced (by approximately 50–60 %) following treatment with 50 μM daidzein, R- or S-equol. Anti-invasive effects were also observed with R-equol at 2.5 and 10 μM though overall equipotent effects were induced by all compounds. Inhibition of invasion induced by all three compounds at 50 μM was associated with the down-regulation of MMP-2, while none of the compounds tested significantly affected the expression levels of MMP-9, TIMP-1 or TIMP-2 at this concentration. Following exposure to media containing 50 μM R- or S-equol for 48-h intracellular concentrations of R- and S-equol were 4.38 ± 1.17 and 3.22 ± 0.47 nM, respectively. Conclusion Daidzein, R- and S-equol inhibit the invasion of MDA-MB-231 human breast cancer cells in part via the down-regulation of MMP-2 expression, with equipotent effects observed for the parent isoflavone daidzein and the equol enantiomers.

Description: Purpose Polydextrose is a low-calorie highly branched-chain glucose polymer that is poorly digested in the upper gastrointestinal tract and therefore demonstrates fibre-like properties. Fibre has been shown to increase satiety and possibly reduce food intake. Therefore, the objective of the current study was to examine the effects of polydextrose on short-term satiety and energy intake. Methods In a repeated-measures randomized blind cross-over design, 26 healthy males consumed a 400-g fruit smoothie containing 12 g (3 %) of polydextrose, and a buffet lunch 60 min after the smoothie. Motivational ratings for satiety and palatability and lunch energy intake were measured. The effects of the polydextrose-containing smoothie were compared against a polydextrose-free control smoothie. Results Polydextrose did not significantly alter the taste and palatability of the fruit smoothie. Consuming the polydextrose-containing smoothie resulted in a significantly lower energy intake at lunch (102 kcal less) compared to the control. Conclusion Polydextrose may be a good fortificant for reducing short-term food intake.

Description: Purpose Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. Methods In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). Results Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (−40 % for PE-spread and −54 % for PE-minidrink, p  〈 0.0001) compared with the control meal. Conclusions PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.

Description: Background Procyanidins are extensively metabolized via phase-II and microbial enzymes. However, their distribution in the body is not well characterized. Aim This study investigates the distribution of procyanidins (monomers and dimers) and their phase-II metabolites in plasma and tissues (thymus, heart, liver, testicle, lung, kidney, spleen and brain). Methods Wistar rats were fed with 1 g of cocoa cream (CC), 50 mg of procyanidin hazelnut skin extract (PE) and 50 mg PE in 1 g CC (PECC). The rats were killed at 0, 1, 1.5, 2, 3, 4 and 18 h after gavage, and the plasma and tissues were analyzed by UPLC–MS/MS. Results Epicatechin–glucuronide was the main metabolite in the plasma after the CC intake, with C max at 423 nM and t max at 2 h, and methyl catechin–glucuronide (301 nM, 2 h) was the main metabolite in the plasma after the PE intake. As a result of the PECC enrichment, epicatechin–glucuronide (452 nM, 1.5 h) and catechin–glucuronide (297 nM, 2 h) were the main metabolites in the plasma. Methyl catechin–glucuronide was found in the liver after PE (8 nmol/g tissue, 4 h) and PECC (8 nmol/g, 1.5 h). The kidney was found to contain a high concentration of phase-II metabolites of procyanidins and is therefore thought to be the main site of metabolism of the compounds. Methyl catechin–sulfate (6.4 nmol/g, 4 h) was only quantified in the brain and after PE intake. Catechin metabolites were not found in the spleen or heart. Phenolic acids were detected in all tissues. Conclusions The formulation of a product enriched or fortified with procyanidins is a way to increase their bioavailability, with clear effects on the plasmatic pharmacokinetics, and a greater accumulation of phenolic metabolites in such tissues as the liver, kidney, lung and brain.

Description: Objective There is increasing evidence that anorexia of aging can cause physical and mental impairment. The aim of the present study was to evaluate the relationship between anorexia and sarcopenia in elderly persons aged 80 years or older. Methods Data are from the baseline evaluation of 354 subjects enrolled in the ilSIRENTE study. The ilSIRENTE study is a prospective cohort study performed in the mountain community living in the Sirente geographic area (L’Aquila, Abruzzo) in Central Italy. We defined anorexia as the presence of loss of appetite and/or lower food intake. According to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, diagnosis of sarcopenia required the documentation of low muscle mass plus the documentation of either low muscle strength or low physical performance. The relationship between anorexia and sarcopenia was estimated by deriving odds ratios from the multiple logistic regression models considering sarcopenia as the dependent variable. Results Nearly 21 % of the study sample showed symptoms of anorexia. Using the EWGSOP-suggested algorithm, 103 subjects (29.1 %) with sarcopenia were identified. Thirty-four (46.6 %) participants were affected by sarcopenia among subjects with anorexia compared to 69 subjects [24.6 %] without anorexia ( p  〈 0.001). After adjusting for potential confounders including age, gender, functional and cognitive impairment, physical activity, urinary incontinence, comorbidity, congestive heart failure, COPD, depression, anti-cholinergic drugs, and TNF-α plasmatic levels, participants with anorexia had a higher risk of sarcopenia compared with non-anorexic subjects (HR 1.88, 95 % CI 1.01–3.51). Conclusions Anorexia is common among community-dwelling older subjects in Italy. Our results suggest that among old–old subjects, anorexia is independently associated with sarcopenia.

Description: Purpose Postprandial metabolic stress as a consequence of ingestion of high-energy meals is recognized as an important risk factor for cardiovascular disease. The objective of this study was to evaluate the inflammatory and antioxidant response of the body to the acute ingestion of a high-fat meal (HFM). Methods Fifteen healthy overweight subjects were recruited for the study. After HFM consumption, plasma glucose, insulin, uric acid (UA), triglycerides (TG), total cholesterol (TC), thiols (SH), inflammatory cytokines (IL-6 and TNF-α) and dietary antioxidants were measured at 0, 0, 5, 1, 2, 4, 6 and 8 h points from ingestion. Results The ingestion of HFM induced significant increases in both TG and TC, with peaks at 4 h ( p  〈 0.001) and 8 h ( p  〈 0.01), respectively. IL-6 and TNF-α significantly increased postprandially, reaching maximum concentrations 8 h after meal consumption ( p  〈 0.001). Whereas plasma concentrations of vitamins and carotenoids were not changed by HFM, SH and UA increased, peaking 2–4 h postingestion ( p  〈 0.001 and 0.01, respectively). Increments of SH and UA were positively correlated with AUC for TG (Pearson coefficient 0.888, p  〈 0.001 and 0.923, p  〈 0.001, respectively). Conclusions Present results indicate that as a consequence of an excess of dietary fat, the body responds through an inflammatory reaction, which is accompanied by an increment of endogenous antioxidant defenses, mediated by UA and SH, but not by vitamins C and E and carotenoids. Although further studies are needed, results of the current investigation represent novel findings on endogenous strategies of redox defense from fat overloads.

Description: Purpose Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids. Methods Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood samples were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids. Results Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns. Conclusion The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.

Description: Purpose Glutamine (Gln) is a nutrient with immunomodulatory effects in metabolic stressed conditions. This study investigated the effects of Gln on colonic-inflammatory-mediator expression and mucosal repair in mice with dextran sulfate sodium (DSS)-induced colitis. Methods C57BL/6 mice received distilled water containing 3 % DSS for 5 d to induce colitis. One of the DSS-treated groups was intraperitoneally injected with an alanyl (Ala)-Gln solution 3 days before (G-DSS) while the other group was administered Ala-Gln 3 days after colitis (DSS-G) was induced. The Ala-Gln solution provided 0.5 g Gln/kg/d. The saline-DSS group (S-DSS) received an identical amount of saline before and after colitis was induced to serve as a positive control. Results The S-DSS group had a shorter colon length, higher plasma haptoglobin level, and more-severe colon inflammation. Also, the toll-like receptor (TLR)4 level, nuclear factor (NF)-κB activation, and inflammatory cytokine gene expression in the colon were higher than those of the normal control group. Gln administration either before or after colitis suppressed TLR4 protein levels, decreased plasma haptoglobin, and reduced colon inflammation. Histological inflammatory scores were also lowered. Compared to the post-colitis Gln group, preventive use of Gln had higher colon length, expressions of mucin 2, trefoil factor 3, and heat shock protein 72 genes were also upregulated in the colon. Conclusions These results suggest that Gln administered either before or after the colitis mitigated inflammation of colitis that was not observed in group without Gln injection. Prophylactic treatment with Gln had more-beneficial effects on reducing inflammatory markers and enhancing the recovery of mucosa in DSS-induced colitis.

Description: Background/Objectives Folate has been strongly implicated in the aetiology of colorectal cancer. However, the relationship between dietary folate intake, rectal mucosal folate status and colorectal cancer risk is uncertain. The study aimed to estimate nutrient intakes and measure systemic folate status and rectal mucosal folate concentration in people at differential risk of developing colorectal cancer. Methods Two hundred and twenty-eight individuals were recruited from gastroenterology clinics and subdivided into three patient groups: untreated colorectal cancer ( n  = 43), adenomatous polyps ( n  = 90) or normal bowel ( n  = 95). Biopsies from macroscopically normal rectal mucosa and blood were collected and used for the measurement of rectal mucosal 5-methyltetrahydrofolate (5-MeTHF) and systemic markers of folate status, respectively. Nutrient intake was estimated using a validated food frequency questionnaire. Results Dietary intake variables, plasma 5-MeTHF and red cell folate and plasma homocysteine concentrations were similar in all three subject groups and 95 % CI fell within normal range for each variable. Rectal mucosal 5-MeTHF concentration was higher in the normal mucosa of adenomatous polyp patients than in normal subjects ( P  = 0.055). Rectal mucosal 5-MeTHF was associated significantly with plasma folate ( P  〈 0.001, r  = 0.294), red cell folate ( P  = 0.014, r  = 0.305), plasma homocysteine ( P  = 0.017, r  = −0.163) and dietary folate intake ( P  = 0.036, r  = 0.152). Conclusions This study demonstrates adequate folate status of patients attending gastroenterology clinics for the investigation of bowel symptoms, with no significant difference in dietary intakes or systemic folate status indices according to diagnosis. Rectal mucosal 5-MeTHF concentrations were elevated in adenomatous polyp patients, but failed to reach significance. Further studies are required to determine the biological significance of this observation.

Description: Purpose An iron intake of 〉2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8–1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term. Methods At term age, 3 and 6 months post-term, ferritin (μg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated. Results Iron was supplemented to 71.7 % of HM-fed and 83.7 % of IFF-fed infants between term age and 3 months post-term and to 13 % of HM-fed and 0 % of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin 〈12 μg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8 % and 26.3 vs. 9.5 %, P  〈 0.02). Conclusion This observational study demonstrates that ferritin 〈12 μg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8–1.0 mg iron/100 ml), as they achieve ferritin ≥12 μg/l without additional iron supplements between 3 and 6 months post-term.

Description: Purpose There is considerable variation in incremental circulating 25-hydroxyvitamin D (25OHD) levels on vitamin D supplements, even when similar age groups and identical vitamin D doses are compared. We therefore aimed to investigate the importance of body weight for the dose–response relation in circulating 25OHD. Methods We performed a systematic review of randomized placebo-controlled vitamin D supplementation trials in all age groups ≥10 years to clarify the influence of body weight and other parameters on incremental circulating 25OHD levels (difference between baseline and in-study values) in vitamin D-deficient and non-deficient individuals. Results We included 144 cohorts from 94 independent studies, published from 1990 to November 2012, in our systematic review. There was a logarithmic association between vitamin D dose per kg body weight per day and increment in circulating 25OHD. In multivariable regression analysis, vitamin D dose per kg body weight per day could explain 34.5 % of variation in circulating 25OHD. Additional significant predictors were type of supplement (vitamin D 2 or vitamin D 3 ), age, concomitant intake of calcium supplements and baseline 25OHD, explaining 9.8, 3.7, 2.4 and 1.9 %, respectively, of the variation in circulating 25OHD. Conclusions This systematic review demonstrates that body weight is an important predictor of variation in circulating 25OHD in cohorts on vitamin D supplements. Our model provides an estimate of the daily vitamin D dose that is necessary for achieving adequate circulating 25OHD levels in vitamin D-insufficient or vitamin D-deficient individuals/cohorts with different body weights and ages.

Description: Purpose German guidelines recommend breast milk as ideal for infant’s nutrition, supporting exclusive breastfeeding for at least 4 months. Moreover, in mothers with insufficient fish intake, DHA status may be improved by supplementation during pregnancy and lactation. However, little is known on current rates of breastfeeding and DHA supplementation in Germany. The objective of this study was to analyse frequencies and demographic determinants of breastfeeding and DHA supplementation in Germany. Methods Data derived from a nationwide consumer survey of 986 mothers with children between 5 and 36 months of age in Germany. Results 78.3 % reported that they ever breastfed their children, and 55.6 % of the mothers exclusively breastfed for at least 4 months. Mothers who did not breastfeed were less likely to be informed by their paediatrician or midwife and were more often not informed at all; 27.8 % of mothers used DHA supplements during pregnancy, 16.8 % postnatal. DHA supplementation was more common in women with a high versus a low fish intake. The social status was the major determinant of breastfeeding initiation and exclusivity and also DHA supplementation. Conclusion Breastfeeding initiation and duration of exclusive breastfeeding in Germany need to be improved. Professional counselling and support, with a focus on mothers from lower social classes, appears necessary to increase current rates of breastfeeding initiation, duration, and exclusiveness, but also to ensure a sufficient supply with DHA in pregnant and lactating women, particularly in women with low fish consumption.

Description: Purpose There is limited prospective evidence at population scale of the impacts of lifestyle and surrogate measures of general and abdominal adiposity on the transition of a metabolically healthy (absence of a metabolic disorder) overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese (MAOO) phenotype. Therefore, we determined the relationship between 10-year body mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and lifestyle changes and the transition of the MHOO phenotype. Methods We conducted a prospective population-based study of 3,052 male and female Spaniards aged 25–74 years who were followed from 2000 through 2009. Diet and leisure-time physical activity were recorded on validated questionnaires. Weight, height, WC, blood lipids, glycemia, and blood pressure were measured. All variables were obtained at baseline (BL) and follow-up (FL). Participants with a BMI ≥ 25 kg/m 2 and free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype. A composite healthy lifestyle index (HLI) was constructed by including temporary changes in 3 lifestyle variables (diet, leisure-time physical activity, and smoking). Results Initially, 20.8 % of subjects had the MHOO phenotype; 49.2 % of these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC, WHtR were positively associated ( p  = 0.004, p  = 0.018, and p  = 0.016, respectively) with this transition. One unit increase in the HLI was associated with a 33 % lower risk ( p  = 0.025) to the MAOO phenotype transition after adjusting for age, sex, educational level, and baseline energy intake, BMI, WC, and WHtR. Conclusions The presence of metabolic disorders in the MHOO phenotype is predicted by an increase in anthropometric surrogate measures of general and abdominal adiposity. In contrast, a healthy lifestyle protects against a transition to the MAOO phenotype.

Description: Background and aims Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are important intestinal neurotransmitters that coexist in the gut enteric nervous system and play an important role in intestinal physiology (e.g., absorption, motility, fluid secretion and smooth muscle relaxation). It is also known that cold exposure alters several aspects of gastrointestinal physiology and induces hyperphagia to meet increased metabolic demands, but there are no data regarding NO and VIP involvement in intestinal response during acclimation to cold. The objective of this study was to determine the influence of long-term l -arginine supplementation on the expression of the three isoforms of nitric oxide synthase (NOS) and VIP in small intestine of rats acclimated to room temperature or cold. Methods Animals (six per group) acclimated to room temperature (22 ± 1 °C) and cold (4 ± 1 °C), respectively, were treated with 2.25 % l -arginine, a substrate for NOSs, or with 0.01 % N ω -nitro- l -arginine methyl ester, an inhibitor of NOSs, for 45 days. The topographical distribution of VIP and NOSs expression in small intestine was studied by immunohistochemistry, and ImageJ software was used for semiquantitative densitometric analysis of their immunoexpression. Results Long-term dietary l -arginine supplementation increases VIP and NOSs immunoexpression at room temperature while at cold increases the endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat small intestine. Conclusion Our results demonstrate that long-term dietary l -arginine supplementation modulates NOSs and VIP immunoexpression in rat small intestine with respect to ambient temperature, pointing out the eNOS as a predominant NOS isoform with an immunoexpression pattern similar to VIP.

Description: Purpose To investigate the effect that wheat bran modified by autoclaving (MWB) had on reducing fat accumulation in hamsters fed a hypercholesterolemia- and obesity-inducing diet. Methods Male hamsters ( n  = 45) were randomized into 3 groups and fed a hypercholesterolemia- and obesity-inducing diet with or without 10 % standard wheat bran or MWB for 28 days. Our outcome measures included body composition measured by DXA, oxygen consumption and plasma lipids and glucose concentrations. Results Animals fed the MWB diet had lower % fat mass (49.8 vs. 53.4 %; p  = 0.02) and higher % lean body mass (47.2 vs. 44.1 %; p  = 0.02) compared with controls despite no differences in food intake or weight gain. Additionally, plasma glucose tended to be lower (6.9 vs. 8.5 mmol/l; p  〈 0.08) in the MWB animals compared with controls. Conclusions Our data suggest that the compositional changes in autoclaved wheat bran, specifically solubility of phenolic antioxidants and fiber, may have contributed to the lower fat accumulation in our animals. Further study is needed to determine whether the exact mechanism involved increased lipolysis and energy utilization from adipose.

Description: Purposes Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2 cells to define the role of adiponectin and its receptor 1 in the development of fatty liver syndrome. Methods and results Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. Conclusion AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

Description: Purpose The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model. Methods Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed. Results All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p  〈 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats. Conclusions This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

Description: Purpose Several countries have recently reported stabilization and/or a decrease in the prevalence of pediatric obesity. However, systematic, repeated national monitoring studies are scarce, and it is unclear whether this trend would be sustained. The objective was to present the latest overweight and obesity prevalence in Swiss children and to investigate trends in prevalence from 1999 to 2012. Methods Using probability-proportionate-to-size cluster sampling, nationally representative samples of children aged 6–12 years were recruited in 1999 ( n  = 594), 2002 ( n  = 2,493), 2004 ( n  = 328), 2007 ( n  = 2,218), 2009 ( n  = 907), and 2012 ( n  = 2,963). Height and weight were measured to calculate BMI (kg/m 2 ). BMI cutoffs proposed by the Centers for Disease Control and Prevention (CDC) and by the International Obesity Task Force were used to determine the prevalence of overweight (excluding obesity) and obesity. Waist circumference was measured in 2007 and 2012, and multiple skinfold thicknesses assessed in 2002 and 2012. Results Using the CDC criteria, prevalences of overweight and obesity in 2012 were 11.9 % (95 % CI 10.7–13.1) and 7.1 % (95 % CI 6.2–8.0), respectively, and did not change between 1999 and 2012 ( β  = −0.144, p  = 0.293 and β  = −0.063, p  = 0.552, respectively). Boys had significantly higher obesity prevalence than girls in 2007 (5.6 vs. 3.4 %) and 2012 (8.1 vs. 5.9 %). Percentage of children with excess waist circumference and body fat percentage did not differ between 2007 and 2012, and 2002 and 2012, respectively. Conclusion Our data indicate the prevalence of childhood adiposity in Switzerland stabilized between 1999 and 2012, but ≈1 in 5 children remain overweight or obese and further efforts are needed to control the epidemic.

Description: Purpose Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Methods Male Wistar rats (180–200 g) were divided into two groups: normal-diet or high-fat-diet ( n  = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups ( n  = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Results Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. Conclusion We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

Description: Purpose Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits. Methods The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet. Results Cysteine fortification in NI rats increased free cysteine ( P  〈 0.0001) and glutathione ( P  〈 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine ( P  〈 0.0007) and free cysteine ( P  〈 0.03) in plasma, and free cysteine ( P  〈 0.02) and glutathione ( P  〈 0.01) in liver. Food intake decreased over time in alanine-fed rats ( r 2  = 0.73, P  = 0.0002), whereas it was constant in cysteine-fed rats ( r 2  = 0.02, P  = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses. Conclusion Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

Description: Background and aim Apoptosis is a major cause of myocyte death, and taurine is anti-apoptotic. Heat shock protein 70 (HSP70) (which is regulated by heat shock factor—HSF-1) is also anti-apoptotic, and caspase 3 stimulates the apoptotic pathway. This study investigated whether taurine affects atherogenic diet-induced myocardial apoptosis, and whether HSP70, HSF-1 and caspase 3 are involved. Methods New Zealand white rabbits were divided into 3 groups for 4 weeks according to their diet. Group 1 (control) was fed a normal rabbit diet; Group 2 (MC) received a normal rabbit diet with 1 % methionine plus 0.5 % cholesterol. Group 3 received MC diet + 2.5 % taurine (MCT). Results The atherogenic diet did not affect myocardial HSP70 or HSF-1 protein, but increased myocardial apoptotic nuclei to 40 % ( p  〈 0.01) versus 7 % in con and 12 % in MCT ( p  〈 0.01). However, in MCT, myocardial HSP70 expression increased by 42.7 % versus con and MC ( p  = 0.016), HSF-1 by 12 % versus con and MC ( p  〈 0.05), and total nuclei count increased by 37 % versus MC ( p  〈 0.05). Caspase 3 subunits remained unchanged in all groups, and HSP70 was increased approximately twofold in endothelial layer of arterioles ( p  = 0.01). Conclusion This study shows that taurine could reduce myocardial apoptotic nuclei and thus confer myocardial cytoprotection via stimulating myocardial HSP70 via HSF-1 and caspase 3-independent mechanisms.

Description: Purpose Coffee and caffeine have been linked to type 2 diabetes mellitus (T2DM). A dose–response meta-analysis of prospective studies was conducted to assess the association between coffee and caffeine intake and T2DM incidence. Methods Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. Dose–response relationship was assessed by restricted cubic spline. Results Compared with the lowest level, the pooled relative risk (95 % CI) of T2DM was 0.71 (0.67–0.76) for the highest level of coffee intake (26 articles involving 50,595 T2DM cases and 1,096,647 participants), 0.79 (0.69–0.91) for the highest level of decaffeinated coffee intake (10 articles involving 29,165 T2DM cases and 491,485 participants) and 0.70 (0.65–0.75) for the highest level of caffeine intake (6 articles involving 9,302 T2DM cases and 321,960 participants). The association of coffee, decaffeinated coffee and caffeine intake with T2DM incidence was stronger for women than that for men. A stronger association of coffee intake with T2DM incidence was found for non-smokers and subjects with body mass index 〈25 kg/m 2 . Dose–response analysis suggested that incidence of T2DM decreased by 12 % [0.88 (0.86–0.90)] for every 2 cups/day increment in coffee intake, 11 % [0.89 (0.82–0.98)] for every 2 cups/day increment in decaffeinated coffee intake and 14 % [0.86 (0.82–0.91)] for every 200 mg/day increment in caffeine intake. Conclusions Coffee and caffeine intake might significantly reduce the incidence of T2DM.

Description: Purpose Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs). Methods Forty male Sprague–Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) ( n  = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food ( n  = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs. Results BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation. Conclusion In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state.

Description: Purpose Previously, it was showed that vegan diet improves the metabolism of triglyceride-rich lipoproteins by increasing the plasma clearance of atherogenic remnants. The aim of the current study was to investigate this metabolism in lacto-ovo vegetarians whose diet is less strict, allowing the ingestion of eggs and milk. Transfer of lipids to HDL, an important step in HDL metabolism, was tested in vitro. Methods Eighteen lacto-ovo vegetarians and 29 omnivorous subjects, all eutrophic and normolipidemic, were intravenously injected with triglyceride-rich emulsions labeled with 14 C-cholesterol oleate and 3 H-triolein. Fractional clearance rates (FCR, in min −1 ) were calculated from samples collected during 60 min. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids. Results LDL cholesterol was lower in vegetarians than in omnivores (2.1 ± 0.8 and 2.7 ± 0.7 mmol/L, respectively,  p  〈 0.05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegetarians than in omnivores (0.016 ± 0.012, 0.003 ± 0.003,  p  〈 0.01), whereas triglyceride FCR was equal. Cholesteryl ester transfer to HDL was lower in vegetarians than in omnivores (2.7 ± 0.6, 3.5 ± 1.5 %,  p  〈 0.05), but free cholesterol, triglyceride and phospholipid transfers and HDL size were equal. Conclusion Similarly to vegans, lacto-ovo vegetarian diet increases remnant removal, as indicated by cholesteryl oleate FCR, which may favor atherosclerosis prevention, and has the ability to change lipid transfer to HDL.

Description: Purpose Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. Methods Premenopausal ( n  = 8) and postmenopausal women ( n  = 8) received 250 mg of olive leaf extract, blood samples ( t  = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. Results Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32 %) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. Conclusions Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.

Description: Purpose This study was carried out to investigate the effect of vitamins E and C on cognitive performance among the elderly in Iran. Methods About 256 elderly with mild cognitive impairment, aged 60–75 years, received 300 mg of vitamin E plus 400 mg of vitamin C or placebo daily just for 1 year. Background Demographic characteristics, anthropometric variables food consumption, cognitive function by Mini-Mental State Examination (MMSE), and some of the oxidative stress biomarkers were examined. Results Antioxidant supplementation reduced malondialdehyde level ( P  〈 0.001) and raised total antioxidant capacity ( P  〈 0.001) and glutathione ( P  〈 0.01). The serum 8-hydroxydeoxyguanosine remained unchanged ( P  〈 0.4). After adjusting for the covariates effects, MMSE scores following 6- (25.88 ± 0.17) and 12-month antioxidant supplementation (26.8 ± 0.17) did not differ from control group (25.86 ± 0.18 and 26.59 ± 0.18, respectively). Conclusion Despite significant improvement in most of the oxidative stress biomarkers, antioxidants’ supplementation was not observed to enhance cognitive performance. A large number of kinetic and/or dynamic factors could be suspected.

Description: Purpose The purpose of the study is to evaluate the effects of creatine supplementation on homocysteine (Hcy) plasma levels after acute exercise in humans. Methods Twenty-three young (under-20) soccer players were divided into 2 groups: creatine (Cr)- and placebo (Pla)-supplemented groups. The supplementation was performed in double-blind controlled manner using creatine or placebo tablets with 0.3 g/kg during 7 days. Before and after 7 days of supplementation, the athletes performed an acute high-intensity sprint exercise (two consecutive running-based anaerobic sprint test protocol consisted in 6 × 35 m sprint with 10 s between them). Blood samples were collected before and after 7 days of supplementation as well as 0 and 1 h after exercise protocol. Results Homocysteine concentration significant increased ( P  〈 0.05) 1 h after acute exercise (18 %). Acute exercise also decreased red blood cell S-adenosylmethionine (SAM) 30 % with no changes in SAM/SAH ratio. Seven days of creatine supplementation were able to increase ( P  〈 0.05) plasma creatine concentration (Pla 130.1 ± 21.7 vs Cr 1,557.2 ± 220.3 μmol/L) as well as decrease ( P  〈 0.05) plasma guanidinoacetic acid (33 %). Controversially, creatine supplementation did not change Hcy plasma level after 7-day supplementation (Pla 6.9 ± 0.2 vs Cr 7.2 ± 0.2 μmol/L) or after acute exercise (Pla 8.2 ± 0.3 vs Cr 8.4 ± 0.3 μmol/L). No changes in plasma vitamin B12 and folate as well as cysteine and methionine were found. Conclusions Seven days of creatine supplementation does not avoid increased plasma Hcy induced by acute sprint exercise in humans.

Description: Purpose Pharmacokinetics and effects on skeletal muscle and physical performance of oral acetylcarnitine and propionylcarnitine are not well characterized. We therefore investigated the influence of oral acetylcarnitine, propionylcarnitine, and carnitine on body carnitine homeostasis, energy metabolism, and physical performance in mice and compared the findings to non-supplemented control animals. Methods Mice were supplemented orally with 2 mmol/kg/day carnitine, acetylcarnitine, or propionylcarnitine for 4 weeks and studied either at rest or after exhaustive exercise. Results In the supplemented groups, total plasma and urine carnitine concentrations were significantly higher than in the control group receiving no carnitine, whereas the skeletal muscle carnitine content remained unchanged. The supplemented acylcarnitines were hydrolyzed in intestine and liver and reached the systemic circulation as carnitine. Bioavailability of carnitine and acylcarnitines, determined as the urinary excretion of total carnitine, was in the range of 19 %. Skeletal muscle morphology, including fiber-type composition, was not affected, and oxygen consumption by soleus or gastrocnemius fibers was not different between the groups. Supplementation with carnitine or acylcarnitines had no significant impact on the running capacity, but was associated with lower plasma lactate levels and a higher glycogen content in white skeletal muscle after exhaustive exercise. Conclusions Oral supplementation of carnitine, acetylcarnitine, or propionylcarnitine in mice is associated with increased plasma and urine total carnitine concentrations, but does not affect the skeletal muscle carnitine content. Despite better preservation of skeletal muscle glycogen and lower plasma lactate levels, physical performance was not improved by carnitine or acylcarnitine supplementation.

Description: Objectives The aim of the present study was to investigate whether the following four markers: vitamin B 12 , selenium, vitamin D, and parvalbumin may be used as compliance markers for fish intake. Methods Blood samples from a randomized cross-over herring intervention study ( n  = 32) were analysed by HPLC and immunochemistry. The criteria were that plasma or serum concentrations of candidate compliance markers after the herring diet should increase significantly compared to starting concentrations. In addition, the reference meat diet should not yield an increase in plasma concentration of the candidate marker. Results Vitamin B 12 and selenium met the set criteria for indicating a correlation between the marker and fish intake with significant increases in serum concentrations at 8.9 % ( p  = 0.008) and 4.6 % ( p  = 0.02), respectively, after a 6-week herring intervention (5 meals a week). Parvalbumin and 25-hydroxy vitamin D 3 levels did not increase significantly after the herring interventions. Conclusions Vitamin B 12 may be suitable as a compliance marker for fish intake. Although selenium also met the criteria, the change in selenium serum concentrations was small compared to the change in vitamin B 12 levels.

Description: Objective We investigated the long-term effect of pre-weaning nutrition on positive and/or adverse regulation of obesity risk and health complications in male Sprague–Dawley rats. Design and subject Two experimental models were used in the present work: (1) To induce postnatal over- or normal nutrition, the litter size was adjusted to 4 (small litters—SL) and to 10 pups (normal litters—NL) in the nest, (2) in suckling pups at day 10, we used cross-fostering to identify the effect of altered dietary environment on their future body fat regulation, food intake, blood pressure, and the duodenal and jejunal alkaline phosphatase activity. After weaning, these control (NL, SL) and cross-fostered (NL–SL, SL–NL) groups were exposed to standard laboratory diet. Results On day 50, the SL in comparison with NL rats became heavier and displayed enhanced adiposity accompanied by significantly increased systolic blood pressure (19 %) and duodenal (16 %) and jejunal (21 %) alkaline phosphatase (AP) activity. The impact of pre-weaning over-nutrition of NL–SL pups was associated with long-lasting positive effect on obesity. In contrast, SL–NL rats submitted until weaning to the opposite normalized feeding condition on day 50 showed significantly decreased fat deposition (21 %), systolic blood pressure (20 %), and AP activity in duodenum and jejunum (14 %). Conclusions These results contribute to a better understanding of how early-acquired dietary habits determine the attenuation or prevention of obesity development in later life and can provide some benefit for optimizing the future dietary strategies in young and adult obese individuals.

Description: Introduction Bladder cancer is the fourth most frequently diagnosed malignancy in males in Córdoba, Argentina. The evidence regarding an association between urinary tract tumors and dietary factors still remains controversial. Argentina has particular dietary habits, which have already been associated with cancer occurrence. Purposes (a) To estimate the association of typical dietary patterns in Argentina on the occurrence of urinary tract tumors and (b) to assess the urban–rural context of residence and cancer occurrence dependency. Methods A case–control study of urinary tract tumors ( n  = 123, 41/82 cases/controls) was performed in Córdoba Province (Argentina), 2006–2011. A two-level logistic regression model was fitted, taking into account rural–urban residence. An exhaustive probabilistic sensitivity analysis (bias analysis) was performed. Results Southern Cone pattern, characterized by red meat, starchy vegetables and wine consumptions (OR 1.75 high versus low level of adherence to the pattern), and a medium adherence to a high-sugar drinks pattern, with high loadings for soft drinks (OR 2.55), were associated with increasing risk of urinary tract tumors. High adherence to the latter pattern was inversely associated (OR 0.72). The occurrence of urinary tract tumors was also linked to place of residence (urban–rural), explaining more than 20 % of outcome variability and improving the above risk estimations. Conclusions A high intake of red meat, starchy vegetables and wine, and a moderate intake of high-sugar drinks seem to be associated with increased risk of urinary tract tumors, with differences related to the context of residence.

Description: Purpose This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined. Methods Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0 % levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase). Results Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg ( p  〈 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant ( p  〈 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly ( p  〈 0.05) suppressed (0.047–0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040–0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL). Conclusions The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

Description: Purpose To evaluate how long-term dietary intake of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs), estimated by repeated food frequency questionnaires (FFQs) over 15 years, is correlated with LCn-3 PUFAs in adipose tissue (AT). Methods Subcutaneous adipose tissue was obtained in 2003–2004 (AT-03) from 239 randomly selected women, aged 55–75 years, after completion of a 96-item FFQ (FFQ-03). All participants had previously returned an identical FFQ in 1997 (FFQ-97) and a 67-item version in 1987–1990 (FFQ-87). Pearson product-moment correlations were used to evaluate associations between intake of total and individual LCn-3 PUFAs as estimated by the three FFQ assessments and AT-03 content (% of total fatty acids). Results FFQ-estimated mean relative intake of LCn-3 PUFAs (% of total fat intake) increased between all three assessments (FFQ-87, 0.55 ± 0.34; FFQ-97, 0.74 ± 0.64; FFQ-03, 0.88 ± 0.56). Validity, in terms of Pearson correlations between FFQ-03 estimates and AT-03 content, was 0.41 (95 % CI 0.30–0.51) for total LCn-3 PUFA and ranged from 0.29 to 0.48 for individual fatty acids; lower correlation was observed among participants with higher percentage body fat. With regard to long-term intake estimates, past dietary intake was also correlated with AT-03 content, with correlation coefficients in the range of 0.21–0.33 and 0.21–0.34 for FFQ-97 and FFQ-87, respectively. The correlations were improved by using average estimates from two or more FFQ assessments. Exclusion of fish oil supplement users (14 %) did not alter the correlations. Conclusion These data indicate reasonable validity of FFQ-based estimates of long-term (up to 15 years) LCn-3 PUFA intake, justifying their use in studies of diet-disease associations.

Description: Purpose Accumulating evidence suggests that inhibitors of aldose reductase (AR) may prevent hyperglycemia-induced long-term complications in diabetes mellitus. In the present study, we evaluated the AR inhibitory potential of ethanolic (EtOH) extracts from 22 seaweed species. Methods AR inhibitory activities of the selected seaweed species were evaluated using the rat lens aldose reductase (RLAR) inhibitory assay. Results All extracts exhibited RLAR inhibitory activity, which ranged from 5.87 to 92.71 % at a concentration of 50 μg/mL. Since Capsosiphon fulvescens exhibited significant inhibitory potential and is a frequently used foodstuff, it was selected for a detailed investigation using RLAR and advanced glycation end products (AGE) formation inhibitory assays. Among the different solvent-soluble fractions, the CH 2 Cl 2 , EtOAc, and n -BuOH fractions showed promising RLAR and AGE formation inhibitory activities. Considering the AR inhibitory potential, CH 2 Cl 2 and EtOAc fractions were selected for chromatographic separation and yielded 11 compounds in which capsofulvesin A, capsofulvesin B, and chalinasterol showed potential RLAR inhibitory activity with the respective IC 50 values of 52.53, 101.92, and 345.27 μM. Kinetic studies revealed that capsofulvesin A and chalinasterol exhibited mixed type inhibition, while capsofulvesin B exhibited noncompetitive inhibition. To our knowledge, this is the first report of AR inhibitory activity of the glycolipids capsofulvesin A and capsofulvesin B. Conclusions Our results clearly indicate the potential RLAR and AGE formation inhibitory activities of C. fulvescens as well as its isolated constituents, which could be further explored to develop therapeutic modalities for the treatment of diabetes and related complications.

Description: Purpose This cohort study investigated the association between sugar-sweetened beverage (SSB) and diet soda consumption and the incidence of type 2 diabetes in Japanese men. Methods The participants were 2,037 employees of a factory in Japan. We measured consumption of SSB and diet soda using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual medical examinations over a 7-year period. Hazard ratios (HRs) with 95 % confidence intervals (CIs) for diabetes were estimated after adjusting for age, body mass index, family history, and dietary and other lifestyle factors. Results During the study, 170 participants developed diabetes. The crude incidence rates (/1,000 person-years) across participants who were rare/never SSB consumers, 〈1 serving/week, ≥1 serving/week and 〈1 serving/day, and ≥1 serving/day were 15.5, 12.7, 14.9, and 17.4, respectively. The multivariate-adjusted HR compared to rare/never SSB consumers was 1.35 (95 % CI 0.80–2.27) for participants who consumed ≥1 serving/day SSB. Diet soda consumption was significantly associated with the incident risk of diabetes ( P for trend = 0.013), and multivariate-adjusted HRs compared to rare/never diet soda consumers were 1.05 (0.62–1.78) and 1.70 (1.13–2.55), respectively, for participants who consumed 〈1 serving/week and ≥1 serving/week. Conclusions Consumption of diet soda was significantly associated with an increased risk for diabetes in Japanese men. Diet soda is not always effective at preventing type 2 diabetes even though it is a zero-calorie drink.

Description: Purpose Iodine is a trace element of thyroid hormones. Excessive or insufficient iodine intake is associated with various thyroid diseases. Urinary iodine (UI) is a sensitive indicator and a recommended barometer of population iodine intake. In Korea, there has been no available data regarding iodine intake in preschool children. We investigated the iodine intake status of Korean preschool children through examination of their UI. Methods This cross-sectional study was performed in 611 healthy preschool children (302 from Seoul and 309 from Masan), aged from 2 to 7 in 2010. UI concentration was measured by inductively coupled plasma-mass spectrometry. Results The median UI concentration was 438.8 μg/L. Insufficient iodine intakes (〈100 μg/L) were seen in 24 children (3.9 %), and excessive iodine ingestion (〉300 μg/L) was found in 406 children (66.4 %). There were no significant differences in UI between different sexes and ages. Additionally, the median UI concentration was higher in children from Seoul (512.2 μg/L) than that in children from Masan (362.4 μg/L, P  〈 0.001). Conclusion About two-thirds of Korean preschool children were in the state of excessive iodine intake, and 3.9 % of children showed insufficient iodine intake. Preventive measures and follow-up for iodine intake in preschool children are needed.

Description: There is growing evidence that early nutrition affects later cognitive performance. The idea that the diet of mothers, infants, and children could affect later mental performance has major implications for public health practice and policy development and for our understanding of human biology as well as for food product development, economic progress, and future wealth creation. To date, however, much of the evidence is from animal, retrospective studies and short-term nutritional intervention studies in humans. The positive effect of micronutrients on health, especially of pregnant women eating well to maximise their child’s cognitive and behavioural outcomes, is commonly acknowledged. The current evidence of an association between gestational nutrition and brain development in healthy children is more credible for folate, n-3 fatty acids, and iron. Recent findings highlight the fact that single-nutrient supplementation is less adequate than supplementation with more complex formulae. However, the optimal content of micronutrient supplementation and whether there is a long-term impact on child’s neurodevelopment needs to be investigated further. Moreover, it is also evident that future studies should take into account genetic heterogeneity when evaluating nutritional effects and also nutritional recommendations. The objective of the present review is to provide a background and update on the current knowledge linking nutrition to cognition and behaviour in children, and to show how the large collaborative European Project NUTRIMENTHE is working towards this aim.

Description: Purpose Caffeine may repair skin damage induced by excessive exposure to ultraviolet light. The purpose of this study was to investigate the association between caffeine intake and incidence of basal cell (BCC) and squamous cell carcinoma (SCC). We also assessed the associations between coffee consumption and incidence of these skin cancers. Methods Caffeine intake and consumption of coffee were estimated from food frequency questionnaires assessed in 1992, 1994, and 1996 among 1,325 randomly selected adult residents of a subtropical Australian community. All histologically confirmed tumours of BCC and SCC occurring between 1997 and 2007 were recorded. Associations with BCC and SCC were assessed using Poisson and negative binomial regression models and were adjusted for confounders including skin type and indicators of past sun exposure. Results There was no association between total caffeine intake and incidence of BCC or SCC. Participants with prior skin cancers, however, had a 25 % lower risk of BCC if they were in the highest tertile of total caffeine intake (equivalent to daily consumption of four cups of regular coffee) compared with the lowest tertile (multivariable RR 0.75; 95 % CI 0.57–0.97, P trend = 0.025). There was no dose–response relationship with SCC. Consumption of neither caffeinated nor decaffeinated coffee was associated with BCC or SCC. Conclusions Among people with prior skin cancers, a relatively high caffeine intake may help prevent subsequent BCC development. However, caffeine intake appears not to influence the risk of SCC.

Description: Background The Czech Republic lacks body composition data for women. Therefore, the purpose of the study was to analyze body composition [body fat mass (BFM), fat-free mass (FFM), body fat percentage (%BFM) and visceral adipose tissue (VAT)] and to evaluate the changes that occur with aging in women aged 18–89 years. We also analyzed anthropometric characteristics of study participants and developed age-specific percentile curves for body composition parameters. Methods A cross-sectional, non‐randomized study was conducted with a sample of 1,970 apparently healthy Czech women. Body composition was measured using a direct segmental multi-frequency bioelectrical impedance analysis (BSM-BIA). Results The mean BFM was 19.7 ± 8.9 kg, and BFM reached its peak in women over 70, at 27.6 ± 8.8 kg. There was a strong correlation between BFM and age ( r  = 0.61; r 2  = 0.37). Fifty percent of the women in the study had a BFM between 13.0 and 25.0 kg. The %BFM ( r  = 0.69; r 2  = 0.47) and VAT ( r  = 0.88; r 2  = 0.77) were also significantly associated with age. The reference range for %BFM was 22.0–35.6 % (25th–75th percentile). The mean FFM was 45.8 ± 5.5 kg, and FFM decreased with age ( r  = −0.27; r 2  = 0.07). Conclusions The results presented in this study showed a statistically significant increase in BFM,  %BFM and VFA as age increased, and the values reached their peak in women over 70. Even when FFM decreased slightly with age, body weight increased because of the increase in BFM.

Description: Objective To evaluate the effects of 5 % weight loss, through diet only or diet plus exercise, on lipid profile, inflammation and endothelial function in obese individuals. Methods In this randomized clinical trial, 48 obese individuals were randomized to either a diet only group (DI) or a diet and exercise group (DI + EXE). Treatment was maintained until 5 % of the initial body weight was lost. At baseline and upon completion, the following parameters were analyzed: total cholesterol and fractions, triglycerides, fibrinogen, von Willebrand factor, high-sensitive C-reactive protein (hs-CRP) and endothelial function (brachial artery flow-mediated vasodilation—FMD). Results Thirteen individuals dropped out before completing the weight loss intervention. The median time required for reduction of 5 % of initial body weight was 79.7 days for the DI group and 65.9 days for the DI + EXE group ( P  = 0.16). In both DI ( n  = 18) and DI + EXE ( n  = 17), total cholesterol (−15.8 ± 4.8 and −10.5 ± 4.9 mg/dL, respectively), triglycerides (−33.8 ± 10.0 and −39.4 ± 10.3 mg/dL, respectively) and hs-CRP (−1.35 ± 0.41 and −0.45 ± 0.43 mg/L, respectively) decreased significantly, and in a similar response (repeated measures ANOVA). Weight loss did not change significantly the fibrinogen and FMD in both groups. Conclusion A 5 % weight loss improves lipid profile and reduces inflammation in obese individuals. Endothelial function did not change significantly. Weight loss has a significant impact on these cardiovascular risk factors, and this is independent of physical training.

Description: Purpose The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training. Methods Sprague–Dawley rats ( n  = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week. Results The AD resulted in a large ( P  〈 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction ( P  〈 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase ( P  〈 0.001) in SREBP-1c and a decrease ( P  〈 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts ( P  〈 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding. Conclusions It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.

Description: Aim To investigate the effects of a neonatal low-protein diet on the number of macrophages in culture and the expression/production of proteins that regulate macrophage fusion in young and adult rats. Methods Male Wistar rats ( n  = 18) were suckled by mothers fed diets containing 17 % protein (controls, C) or 8 % protein (undernourished, UN). All rats were fed a normal protein diet after weaning. Bronchoalveolar lavage was collected from 42-, 60- and 90-day-old rats. Alveolar macrophages were cultured for 4 days to assess the number of cells and the expression of cadherins, key proteins involved in macrophage fusion, by western blotting. IL-4 and IFN-γ levels in culture supernatants were measured by ELISA. Results Offspring from mothers fed a low-protein diet showed a lower body weight gain. The number of cells in cultured macrophages from UN was reduced at 42 and 60 days and increased at 90 days. IL-4 production was increased in the supernatants from UN group at 60 days but did not affect the expression of cadherins. IFN-γ production was increased in the supernatants from UN group at 42 and 60 days and reduced at 90 days. Conclusions This study thus demonstrated that dietary restriction during lactation altered the number of alveolar macrophages in culture and the production of fusion proteins of offspring aged 42, 60 or 90 days but did not modify the expression of adhesion molecules important for the fusion of these cells.

Description: Purpose Some studies have suggested an increased risk of breast cancer associated with elevated fasting serum glucose in nondiabetic subjects. Given how common both breast cancer and impaired glucose tolerance are in our aging societies, this is an important issue for public health. Methods We performed a systematic review of prospective cohort studies that examined the association between elevated serum glucose levels in nondiabetic subjects (levels below 7.0 mml/L) and the subsequent risk of breast cancer. We performed a systematic literature search and extracted relevant data in a standard way. We then computed summary relative risks (SRR) and 95 % confidence intervals using a random effects model applied on the risk of highest versus lowest quantile of serum glucose concentrations. Results Ten cohort studies were retrieved. The SRR for all studies was 1.11 (1.00–1.23), with no evidence of heterogeneity or publication bias. The SRR was not affected when the analysis was restricted to the 8 studies that reported results for fasting subjects (SRR = 1.11; 95 % CI 0.98–1.25). Three studies provided BMI-unadjusted and BMI-adjusted SRRs of 1.24 (95 % CI 0.60–2.56) and 1.20 (95 % CI 0.63–2.27), respectively. Similar magnitudes of associations were observed in sensitivity analyses, but statistical significance was lost. Conclusion In nondiabetic subjects, the risk of breast cancer associated with fasting serum glucose levels seems to be small. Potential limitations to this meta-analysis include the fact that not all studies reported risks adjusted for adiposity and that serum glucose levels of comparison groups were variable across studies.

Description: Purpose We investigated effects of ground whole flaxseed supplementation on erythrocyte polyunsaturated fatty acids (PUFAs) and serum biomarkers of inflammation, endothelial dysfunction, oxidative stress, and thrombosis in Chinese with risk factors of metabolic syndrome (MetS). Methods This study was a secondary analysis of a 12-week, randomized, parallel-group trial in participants screened for MetS. The analysis included only those with 2 or more components of MetS before receiving either lifestyle counseling (LC, n  = 90) or LC + 30 g/day flaxseed supplementation (LCF, n  = 83). Results Compared to the LC group, those in the LCF group experienced significant increases in total erythrocyte n-3 PUFAs, α-linolenic acid, eicosapentenoic acid, and docosapentenoic acid (all P 〈 0.001), while total n-6 PUFAs ( P  〈 0.05) and n-6/n-3 ratio decreased ( P  〈 0.001). Arachidonic acid increased significantly in the LC group ( P  〈 0.001), and serum high-sensitivity C-reactive protein, interleukin-18, soluble intracellular adhesion molecular-1, E-selectin, and plasminogen activator inhibitor-1 declined significantly in both groups (all P  〈 0.05), but no between-group differences were observed. There was no significant change in serum interleukin-6, tumor necrosis factor-α, soluble vascular adhesion molecular-1, monocyte chemoattractant protein-1, and oxidized low-density lipoprotein in either group. Conclusions These data suggest that flaxseed supplementation increases erythrocyte n-3 PUFAs, decreases n-6 PUFAs and n-6/n-3 ratio in participants with risk factors of MetS, but has no additional benefits beyond the lifestyle consulting for the multiple biomarkers tested in the current study.

Description: Purpose The objective of the study is to assess the goodness of fit for the diagnosis of metabolic syndrome in adults of four models with different measures of adiposity using confirmatory factor analysis, to develop a cardio metabolic risk index and to analyze its relationship to physical activity. Methods Cross-sectional descriptive multicenter study including 636 patients from the EVIDENT study. Considering as fixed variables, triglycerides/HDL-C ratio, HOMA-IR index and mean arterial pressure, we will compare which single-factor model of metabolic syndrome shows better goodness of fit. The models only differ by the measure of adiposity used: waist circumference, waist circumference/height, body mass index or adiposity index. With the factorial weights obtained, we created a quantitative metabolic index and analyzed its relationship to physical activity, quantified with the accelerometer for 1 week and measured at counts/min. Results The single-factor model including waist circumference in women and body mass index in men were those that were better indicators of goodness of fit. The estimated quantitative metabolic index shows a mean value in men of −0.022 ± 1.29 with a range of values between −3.36 and 4.57 and in women of 0.0001 ± 1.53 with a range of values between −3.17 and 5.55. The quantitative index shows an inverse relationship to physical activity. Conclusions Waist circumference in women and body mass index in men are the measures of adiposity that were better indicators goodness of fit. This quantitative index may be useful to quantify the risk of metabolic syndrome in clinical practice.

Description: Purpose The aim of this study was to evaluate the effect of white cabbage and sauerkraut juices of different origin and indole-3-carbinol (I3C) and diindolylmethane (DIM) on expression of CYP19 gene encoding aromatase, the key enzyme of estrogen synthesis. Methods Human breast cell lines (MCF7, MDA-MB-231 and MCF10A) were examined to compare the action of cabbage juices versus their active components (I3C, DIM). Real-time PCR and Western blot were used in order to analyse CYP19 mRNA and protein, respectively. Results Remarkable differences in the effect on CYP19 transcript and protein level were found between the cabbage juices (in 2.5–25 mL/L concentrations) and indoles (in 2.5–50 μM doses) in the three cell lines. While cabbage juices at the lower doses diminished the aromatase expression in nontumorigenic/immortalized MCF10A breast cells (0.25–0.86-fold change, P  〈  0.05 ), I3C and DIM were more efficient in decreasing the aromatase expression in estrogen-dependant MCF7 breast cancer cells (0.24–0.82-fold change, P  〈  0.05 ). Inhibition of aromatase by juice obtained from cabbage grown on industrial farm was correlated with the induction of apoptosis (1.7–1.8-fold change, P  〈  0.01 ) in MCF10A cells. In estrogen-independent MDA-MB-231 cells, up-regulation of CYP19 expression by I3C and DIM (1.5–2.0-fold change, P  〈  0.05 ) was observed. Similarly, in MCF7 cells juices increased aromatase expression (1.1–2.2-fold change, P  〈  0.05 ). Conclusion These results, particularly that obtained in nontumorigenic/immortalized MCF10A cells, suggest that chemopreventive activity of cabbage against breast cancer observed in epidemiological studies may be partly explained by inhibition of the aromatase expression.

Description: Background Riboflavin is an essential component of the human diet, with an established role for its derivative cofactors in oxidative metabolism. Our previous in vivo data suggest that riboflavin may act as a signalling molecule in the intestinal lumen, regulating crypt development and cell turnover. Our in vitro studies in riboflavin-depleted intestinal cells in culture indicate that riboflavin depletion impairs normal mitosis. Methods The aim of the study was to establish an improved intestinal cell model of riboflavin depletion using the structural analogue of riboflavin, lumiflavin (7,8,10-trimethyl-isoalloxazine) and to determine effects on cell function. The study was conducted using three intestinal cell lines, Caco-2, HCT116 and HT29 cells. Results Cell growth was inhibited in all three cell lines, in a lumiflavin concentration-dependent manner. Riboflavin depletion was confirmed through a significant decrease in intracellular riboflavin concentrations in Caco-2 and HT29 cell lines and a significant increase in the activation coefficient for the flavin adenine dinucleotide-dependent enzyme glutathione reductase. Riboflavin depletion led to a significant reduction in intracellular ATP concentration, and an enhanced generation of reactive oxygen species was also observed in response to riboflavin depletion, in all cell lines; effects were at least fivefold greater in Caco-2 cells than other cells. Riboflavin-depleted Caco-2 and HCT116 cells also showed an irreversible loss of proliferative potential. Conclusions A model system of intracellular riboflavin depletion in intestinal epithelial cells has been developed. Riboflavin depletion induced by lumiflavin results in oxidative stress and a disruption of energy generation, which may contribute to observed effects on cell proliferation.

Description: Purpose The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA through its hypoglycemic effect lowers O -GlcNAcylation which influences the expression and activities of antioxidant enzymes which assume important roles in preventing diabetes-induced oxidative renal injury. Methods An experimental model of diabetes was induced in rats by the administration of 40 mg/kg streptozotocin (STZ) intraperitoneally (i.p.) for five consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. Results An improved glycemic status of LA-treated diabetic rats was accompanied by a significant suppression of oxidative stress and a reduction of oxidative damage of lipids, proteins and DNA. LA treatment normalized CuZn-superoxide dismutase (SOD) and catalase activities in renal tissue of diabetic rats. These changes were allied with upregulated gene expression and lower levels of O -GlcNA glycosylation. The accompanying increase in MnSOD activity was only linked with upregulated gene expression. The observed antioxidant enzyme gene regulation was accompanied by nuclear translocation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), enhanced expression of heat shock proteins (HSPs) and by reduction in O -GlcNAcylation of HSP90, HSP70, and extracellular regulated kinase and p38. Conclusion α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O -GlcNAc-dependent mechanism.

Description: Background and purpose Agar contains a high amount of soluble fibre and has been shown to delay gastric emptying (GE) without impacting on glycaemic response (GR). The current study aimed to further the limited data on the effect of agar on metabolism by assessing the effects on GE and GR as well as appetite- and diet-induced thermogenesis (DIT). Methods In this randomized control trial, eleven healthy volunteers were tested on two occasions following an overnight fast. Following baseline and resting measurements, volunteers were either fed a fruit-flavoured drink (liquid) or consumed a fruit-flavoured jelly (jelly). The two were exactly the same in composition except the jelly contained 4 g of agar crystals. Both contained 50 g of available carbohydrate. DIT was measured using indirect calorimetry, GE using the 13 C sodium acetate breath test, appetite using visual analogue scale and GR using finger prick blood samples. Results The jelly significantly delayed GE across all time points—latency phase ( p  = 0.07), lag phase ( p  = 0.04), half-time ( p  〈 0.0001), ascension time ( p  = 0.025). The jelly also increased all appetite parameters—hunger ( p  = 0.006), fullness ( p  = 0.035), desire to eat ( p  = 0.03) and prospective consumption ( p  = 0.011). However, there were no significant differences in either GR or postprandial DIT between the liquid and jelly. Conclusion Agar delays GE and increases appetite but does not change GR or DIT most probably due to the increase in viscosity caused by the agar jelly.

Description: Purpose To report on plasma/serum levels of antioxidant vitamin and carotenoids in older adults resident in multiple countries in Europe and examine relationships with potential modifiers. Methods Population-based cross-sectional European Eye Study in 7 centres from northern to southern Europe. In total, 4,133 participants aged 65 years or over, collected by random sampling, were recruited. Questionnaires relating to diet, lifestyle and medical history were administered. Non-fasting blood samples were analysed in a single laboratory for vitamins A, C and E and a panel of carotenoids. Associations were analysed by bootstrapped multivariable regression analysis. Results Centre and season influenced the serum and plasma concentrations of all antioxidant vitamins and carotenoids. Gender, BMI, smoking, age, education, alcohol consumption and supplement use were also significantly associated with some, but not all, of the antioxidant vitamins and carotenoids examined. The proportion of variance explained ranged from 4.8 % for retinol to 25.2 % for zeaxanthin. Conclusions In older people, antioxidant vitamin and carotenoid status varies by centre and season, but is also associated with other behavioural and lifestyle variables. Studies aiming to demonstrate an association between antioxidant vitamins and carotenoid status and chronic disease risk should consider these potential confounders.

Description: Background Acrylamide is a chemical compound present in tobacco smoke and food, classified as a probable human carcinogen and a known human neurotoxin. Acrylamide is formed in foods, typically carbohydrate-rich and protein-poor plant foods, during high-temperature cooking or other thermal processing. The objectives of this study were to compare dietary estimates of acrylamide from questionnaires (DQ) and 24-h recalls (R) with levels of acrylamide adduct (AA) in haemoglobin. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC) study, acrylamide exposure was assessed in 510 participants from 9 European countries, randomly selected and stratified by age, sex, with equal numbers of never and current smokers. After adjusting for country, alcohol intake, smoking status, number of cigarettes and energy intake, correlation coefficients between various acrylamide measurements were computed, both at the individual and at the aggregate (centre) level. Results Individual level correlation coefficient between DQ and R measurements ( r DQ,R ) was 0.17, while r DQ,AA and r R,AA were 0.08 and 0.06, respectively. In never smokers, r DQ,R , r DQ,AA and r R,AA were 0.19, 0.09 and 0.02, respectively. The correlation coefficients between means of DQ, R and AA measurements at the centre level were larger ( r  〉 0.4). Conclusions These findings suggest that estimates of total acrylamide intake based on self-reported diet correlate weakly with biomarker AA Hb levels. Possible explanations are the lack of AA levels to capture dietary acrylamide due to individual differences in the absorption and metabolism of acrylamide, and/or measurement errors in acrylamide from self-reported dietary assessments, thus limiting the possibility to validate acrylamide DQ measurements.

Description: Purpose Hyperhomocysteinemia is well recognized as an independent risk factor for the development of premature atherosclerosis. Atherosclerosis, however, may be prevented by polyphenols, potent antioxidant compounds with anti-atherogenic properties. Previously, we used cystathionine beta synthase-deficient mice [Cbs (±)] fed a high-methionine diet—a murine model of hyperhomocysteinemia—to show that daily intake of a red wine polyphenolic extract, mainly comprised of catechin and epicatechin, has a beneficial effect on aortic expression of endothelial dysfunction biomarkers and pro-inflammatory cytokines. The aim of the present study was to understand whether catechin and epicatechin, in purified forms, have anti-atherogenic effects in hyperhomocysteinemia. Methods Cbs (±) mice received 50 μg of catechin and/or epicatechin daily in drinking water for 1 month. Plasma homocysteine (Hcy) level and aortic expression of several endothelial dysfunction biomarkers (Vcam-1, Icam-1, E-selectin, and Lox-1) and pro-inflammatory cytokines (Tnf-α, Il-6) were assessed. Results We found that both catechin and epicatechin had a beneficial effect on plasma homocysteine levels and endothelial dysfunction biomarker expression; however, only catechin had a beneficial effect on pro-inflammatory cytokine expression. Further, when both polyphenols were given, a beneficial effect was observed only on pro-inflammatory cytokine expression. Conclusions Catechin seems to be a more potent anti-atherogenic compound than epicatechin in hyperhomocysteinemia and should be considered as a novel therapeutic approach against endothelial dysfunction induced by this condition.

Description: Purpose Although overweight is an important determinant of diabetes risk, it remains unclear whether food choices can still influence the risk for type 2 diabetes in overweight persons. In this paper, we aim to clarify the role of dietary patterns in the development of type 2 diabetes in overweight and obese individuals. Methods We studied 20,835 overweight and obese participants in the Dutch part of the European Investigation into Cancer and Nutrition (EPIC-NL) study. Dietary intake was measured using a validated food frequency questionnaire, and dietary patterns were generated using factor analysis. Incident type 2 diabetes was verified against medical records. Cox proportional hazards models were used to assess the association between the dietary patterns (factor scores categorized in quartiles) and incident type 2 diabetes. Results Scoring on Pattern 1, characterized by fish, wine, chicken, raw vegetables and fruit juices, was not associated with type 2 diabetes risk after confounder adjustment. A high score on Pattern 2, characterized by soft drinks, fries and snacks, was associated with higher risk of type 2 diabetes (HR Q4 vs. Q1 (95 % CI): 1.70 (1.31; 2.20), p trend  ≤ 0.0001), particularly among less active individuals [less active: HR Q4 vs. Q1 (95 % CI): 2.14 (1.48; 3.09), p trend  = 0.00004, more active: HR Q4 vs. Q1 (95 % CI): 1.35 (0.93; 1.97), p trend  = 0.01; p interaction  = 0.02]. Conclusions A high score on a pattern high in soft drinks, fries and snacks and low in fruit and vegetables was associated with higher risk of type 2 diabetes in overweight and obese subjects especially among physically less active individuals.

Description: Purpose To examine the effect of different dietary fat types on osteopontin (OPN) expressions and inflammation of adipose tissues in diet-induced obese rats. Methods Male Sprague–Dawley rats were randomly assigned to one control group fed standard diet (LF, n  = 10) and two high-fat diet groups fed isoenergy diet rich in lard or soybean oil (HL or HS, n  = 45 each). Diet-induced obese rats in HL and HS group were then subdivided into two groups either continuously fed high-fat diet or switched to low-fat diet for 8 more weeks. Fasting serum glucose, insulin, and OPN concentrations were assayed and QUICKI was calculated; the expression of OPN, IL-6, IL-10, TNF-α, NF-κB, and F4/80 in adipose tissue was determined. Results Both high-fat diets lead to comparable development of obesity characterized by insulin resistance and adipose tissue inflammation. Obese rats continuously fed high-fat diet rich in lard oil exhibited the highest fasting serum insulin level and adipose tissue OPN, F4/80, TNF-α, and NF-κB expression level. In both high-fat diet groups, switching to low-fat diet resulted in less intra-abdominal fat mass, decreased expression of F4/80, TNF-α, and NF-κB, while decreased OPN expression was only observed in lard oil fed rats after switching to low-fat diet. Conclusions Reducing diet fat or replacing lard oil with soybean oil in high-fat diet alleviates obesity-related inflammation and insulin resistance by attenuating the upregulation of OPN and macrophage infiltration into adipose tissue induced by high-fat diet.

Description: Objective The mechanism action of the polyphenol-rich extracts from berries of Aronia melanocarpa (black chokeberry) and from grape seeds in the defence against homocysteine (Hcy) and its derivatives action in blood platelets is still unknown. In this study, the influence of the aronia extract and grape seeds extract (GSE) on the platelet adhesion to collagen and fibrinogen and the platelet aggregation during a model of hyperhomocysteinemia was investigated. The aim of our study in vitro was also to investigate superoxide anion radicals (O 2 −• ) production after incubation of platelets with Hcy, HTL and the aronia extract and GSE during a model of hyperhomocysteinemia (induced by reduced form of homocysteine at final dose of 100 μM) and the most reactive form of Hcy—its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). Moreover, the additional aim of our study was also to establish and compare the influence of the aronia extract, GSE and resveratrol (3,4′,5-trihydroxystilben), a phenolic compound, which has been supposed to be beneficial for the prevention of cardiovascular events, on selected steps of platelet activation. Methods The effects of tested extracts on adhesion of blood platelets to collagen and fibrinogen were determined according to Tuszynski and Murphy. The platelet aggregation was determined by turbidimetry method using a Chrono-log Lumi-aggregometer. Results We have observed that HTL, like its precursor—Hcy stimulated the generation of O 2 −• (measured by the superoxide dismutase—inhibitable reduction of cytochrome c) in platelets and caused an augmentation of the platelet adhesion and aggregation induced by the strong physiological agonist—thrombin. Our present results in vitro also demonstrated that the aronia extract and grape seeds extract reduced the toxicity action of Hcy and HTL on blood platelet adhesion to collagen and fibrinogen, the platelet aggregation and superoxide anion radicals production in platelets, suggesting its potential protective effects on hemostasis during hyperhomocysteinemia. Conclusion In the comparative studies, the aronia extract was found to be more effective antiplatelet factors, than GSE or resveratrol during a model of hyperhomocysteinemia. It gives hopes for development of diet supplements, which may be important during hyperhomocysteinemia.

Description: Purpose The present study investigated the underlying mechanism associated with the hypocholesterolemic activity of blueberry anthocyanins by examining its effect on fecal sterol excretion and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. Methods Hamsters were divided into three groups and fed a 0.1 % cholesterol diet containing 0 % (CTL), 0.5 % (BL), and 1.0 % (BH) blueberry anthocyanins, respectively, for six weeks. Plasma total cholesterol (TC), triacylglycerols (TAG), and non-high-density lipoproteins cholesterol (non-HDL-C) were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. GC analysis was used to quantify hepatic cholesterol and fecal acidic and neutral sterols. Results Dietary supplementation of 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6–12 % in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 22–29 % and 41–74 %, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of NPC1L1, ACAT-2, MTP, and ABCG 8. In addition, blueberry anthocyanins were also able to down-regulate the gene expression of hepatic HMG-CoA reductase. Conclusion The cholesterol-lowering activity of blueberry anthocyanins was most likely mediated by enhancing the excretion of sterols accompanied with down-regulation on gene expression of intestinal NPC1L1, ACAT-2, MTP, and ABCG 8.

Description: Purpose To investigate the role of octreotide, a somatostatin (SST) analog with anti-inflammatory effects, on the digestive and absorptive functions of jejunum in rats fed a high-fat diet, as well as its therapeutic prospects for diet-induced obesity. Methods Rats were divided into three groups with different diet and treatment for the 176-day experiment: (1) control, 18 rats fed with standard chow, (2) high-fat control, 19 rats fed with high-fat chow, and (3) high-fat octreotide, 21 rats fed with high-fat chow and treated with octreotide for the last 8 days of the experiment. Plasma tumor necrosis factor-α (TNF-α) was measured by ELISA and SST by radioimmunoassay. Disaccharidase activity in the jejunal homogenate was determined. SST and Na + -dependent glucose transporter 1 (SGLT-1) in the jejunal mucosa were visualized by immunohistochemistry. SGLT-1 was quantified by reverse transcription polymerase chain reaction and Western blot assays. Results After 176 days, the fat/body weight ratio, villus height, maltase, SGLT-1, and plasma TNF-α in the high-fat control rats were much higher than those in the control rats ( p  〈 0.01 or p  〈 0.05) and were significantly lower in the high-fat + octreotide rats ( p  〈 0.01 or p  〈 0.05). SST levels were dramatically different in the intestinal mucosa of the two high-fat groups (231.12 ± 98.18 pg/mg in the high-fat controls and 480.01 ± 286.65 pg/mg in the octreotide group). Conclusions The low-grade inflammation induced by high-fat diet apparently reduced the secretion of intestinal SST, which increased intestinal absorption of energy and nutrients and formation of adipose tissues. Octreotide effectively reversed this process, a finding that has far-reaching significance for the regulation of energy balance.

Description: Purpose The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B (NF-κB) activation in the liver, yet the mechanism remains unclear. We investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF-κB signaling in the liver of rats fed a GGOH-supplemented diet. Methods Rats were fed a diet supplemented with or without GGOH for 10 days. Rats were then intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the liver damage indicators alanine and aspartate aminotransferases (ALT and AST) were assessed. Liver mRNA and proteins were assayed for changes in NF-κB target genes and signal transduction genes. Results Rats fed a high-dose, GGOH-supplemented diet showed significantly lower levels of plasma inflammatory cytokines and ALT and AST activities. In the liver, GGOH significantly suppressed NF-κB activation and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH supplementation substantially suppressed mRNA expression of signal transducer genes upstream of the IκB kinase complex. Western blotting of liver extracts further demonstrated the substantial decrease in total IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower signal transduction and inhibition of NF-κB after LPS. Conclusion A 10-day, high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced inflammation and activation of NF-κB in rat livers. GGOH significantly modulated NF-κB signaling molecules, inhibiting its signal transduction and activation in the liver, thus protecting against liver damage.

Description: Purpose Phosphate (Pi) salts, often mono- (MP) or polyphosphates (PP), are commonly used as additives in the food industry. Previous studies have shown that the effects of MP and PP on calcium (Ca) and phosphorus (P) metabolism may differ. The aim of this study was to determine whether the effects of MP and PP salts differ on markers of Ca and P metabolism in young women. Methods Fourteen healthy women 19–31 years of age were randomized into three controlled 24-h study sessions, each subject serving as her own control. During each session, the subjects received three doses of MP, PP or a placebo with meals in randomized order. Both Pi salts provided 1,500 mg P/d, and the diet during each session was identical. Markers of Ca and P metabolism were followed six times over 24 h. Results During both MP and PP sessions, we found an increase in serum phosphate (S-Pi, p  = 0.0001), urinary phosphate (U-Pi, p  = 0.0001) and serum parathyroid hormone (S-PTH, p  = 0.048 MP, p  = 0.012 PP) relative to the control session. PP decreased U-Ca more than did MP ( p  = 0.014). Conclusions The results suggest that PP binds Ca in the intestine more than does MP. Based on the S-Pi, U-Pi and S-PTH results, both Pi salts are absorbed with equal efficiency. In the long run, increased S-PTH, caused by either an MP or PP salt, could have negative effects on bone metabolism.

Description: Purpose Elevated circulating activities of alanine aminotransferase (ALT), a marker for liver injury, and the lifestyle of a higher rate of eating in healthy and preclinical subjects are associated with increased risk of obesity and diabetes. In this study, we examined the associations between self-reported rate of eating and circulating ALT activity in middle-aged apparently healthy Japanese men. Methods We conducted a cross-sectional study of 3,929 apparently healthy men aged 40–59 years (mean ± SD age, 49.2 ± 5.8 years; BMI, 23.5 ± 2.8 kg/m 2 ) who participated in health checkups in Japan. We analyzed their clinical serum parameters and lifestyle factors, including self-reported rate of eating. Associations between self-reported rate of eating and liver injury markers [ALT, γ-glutamyl transpeptidase (GTP), and aspartate aminotransferase (AST)], other clinical parameters or lifestyle factors were determined using analysis of variance followed by Tukey’s test. Multivariate logistic regression analyses (MLRA) were performed with ALT activity as the dependent variable and independent variables that included self-reported rate of eating. Results MLRA showed that ALT activity showed trends for higher self-reported rate of eating after adjustment for age, energy intake, and smoking status. The association between ALT activity and self-reported rate of eating disappeared after adjustment for BMI. Conclusion The results of this study show that ALT activity is positively associated with self-reported rate of eating in middle-aged apparently healthy Japanese men.

Description: Purpose To distinguish between contributions to dementia made by homocysteine, folate, B12 and antioxidant micronutrients. Methods This is a follow-up study of a sample reported in 2002. Homocysteine was measured at baseline in 201 individuals born in 1921 and without dementia at age 77 years and followed up to age 88 years. Baseline macro- and micronutrient status was estimated from BMI, the MONICA food frequency questionnaire, plasma folate, B12 and, in a subgroup ( N  = 173), plasma antioxidant micronutrients. Time to dementia onset during follow-up was compared between participants grouped by homocysteine concentration using Cox regression. Model 1 adjusted for age, sex, childhood IQ, education, socioeconomic deprivation, presence of heart disease, hypertension, plasma folate and B12. In model 2 plasma, antioxidants were added to these covariables. Results During a mean follow-up of about 5 years, there were 39 incident dementia cases among 201 participants. In model 1, being in the highest homocysteine group (〉14 μmol/L) was associated with a 234 % increased risk (HR 3.34, 95 % CI 1.16–9.57) of any dementia. After inclusion of plasma antioxidants in model 2, there were 32 incident dementia cases from a subsample ( N  = 173). Homocysteine 〉14 μmol was associated with a 272 % increased dementia risk (HR = 3.72, 95 % CI 1.06–13.08). Conclusions High homocysteine increases the risk of dementia. The association between tHcy and dementia is independent of plasma folate, B12 and antioxidant micronutrient status.

Description: Purpose It is demonstrated that aerobic exercise plays an important role in weight loss programs for obesity by increasing 24 h metabolic rate. While aerobic exercise can result in health and fitness benefits in obese subjects, also independently of weight loss, not completely clear are the effects of bouts of hard exercise on metabolic outcomes. The aim of this study was to test the hypothesis that short-term aerobic activity with anaerobic bouts might result in a greater improvement in the management of obesity than aerobic activity alone. Methods We studied 16 obese subjects (eight men) during a progressive cycloergometric test up to exhaustion, before and after 4 weeks of two different training schedules (6 days/week). Insulin and glycaemia, non-esterified fatty acids (NEFA) and lactic acid were sampled. Group A (eight subjects, four men) performed an aerobic cycle workout; Group B (eight subjects, four men) performed a 25 min aerobic workout followed by 5 min of anaerobic workout. All the subjects maintained their individual eating habits. Results The post-training test showed a decrease in AUCs NEFA in Group A ( p  〈 0.05) and an increase in Group B ( p  〈 0.05), together with an increase in lactic acid in Group A and a decrease in Group B ( p  〈 0.01). β-cell function (HOMA2-B) revealed a reduction only in Group A ( p  〈 0.05). Group B achieved a greatest reduction in body fat mass than Group A ( p  〈 0.05). Conclusions Aerobic plus anaerobic training seem to produce a greater response in lipid metabolism and not significant modifications in glucose indexes; then, in training prescription for obesity, we might suggest at starting weight loss program aerobic with short bouts of anaerobic training to reduce fat mass and subsequently a prolonged aerobic training alone to ameliorate the metabolic profile.

Description: Purpose Aquaporin-1 (AQP1) is the predominant water channel in the heart, linked to cardiovascular homeostasis. Our aim was to study cardiovascular AQP1 distribution and protein levels during osmotic stress and subsequent hydration during postnatal growth. Methods Rats aged 25 and 50 days were divided in: 3d-WR: water restriction 3 days; 3d-WAL: water ad libitum 3 days; 6d-WR+ORS: water restriction 3 days + oral rehydration solution (ORS) 3 days; and 6d-WAL: water ad libitum 6 days. AQP1 was evaluated by immunohistochemistry and western blot in left ventricle, right atrium and thoracic aorta. Results Water restriction induced a hypohydration state in both age groups (40 and 25 % loss of body weight in 25- and 50-day-old rats, respectively), reversible with ORS therapy. Cardiac AQP1 was localized in the endocardium and endothelium in both age groups, being evident in cardiomyocytes membrane only in 50-day-old 3d-WR group, which presented increased protein levels of AQP1; no changes were observed in the ventricle of pups. In vascular tissue, AQP1 was present in the smooth muscle of pups; in the oldest group, it was found in the endothelium, increasing after rehydration in smooth muscle. No differences were observed between control groups 3d-WAL and 6d-WAL of both ages. Conclusion Our findings suggest that cardiovascular AQP1 can be differentially regulated in response to hydration status in vivo, being this response dependent on postnatal growth. The lack of adaptive mechanisms of mature animals in young pups may indicate an important role of this water channel in maintaining fluid balance during hypovolemic state.

Description: Purpose Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.30 g/kg lean body mass), or a non-caloric control after heavy resistance exercise on protein turnover and mRNA expressions of forkhead homeobox type O (FOXO) isoforms, muscle RING finger 1 (MuRF1), and Atrogin1 in young healthy males. Methods Protein turnover was determined by stable isotope-labeled leucine and femoral arteriovenous blood samples at rest and during 6-h recovery. Muscle biopsies were collected at −60 min (rest) and at 60, 210, and 360 min in the recovery period. Results During recovery, leucine NB was significantly higher in the protein groups compared to control ( P  〈 0.001). Differences in leucine NB, rate of disappearance, and oxidation were observed in the early recovery period between whey and caseinate. FOXO1A and MuRF1 were upregulated at 60 and 210 min, and, in contrast, FOXO3 and Atrogin1 were downregulated at 210 and 360 min. For leucine rate of appearance and all FOXO and atrogene mRNA expressions, no differences were observed between groups. Conclusions Whey and caseinate were equally superior to control in the 6-h recovery period and displayed temporal differences with whey having a fast and superior effect in the early part of the recovery period. Effects on mRNA expressions indicate different regulatory mechanisms on the ubiquitin ligases MuRF1 and Atrogin1 in recovery from heavy resistance exercise.

Description: Purpose This study determined whether calcium co-ingestion potentiates postprandial GIP 1–42 and GLP-1 concentrations in humans and the concomitant impact on insulin, appetite sensations and substrate metabolism. Methods Ten healthy males consumed two energy- and macronutrient-matched meals in a double-blind, randomized, crossover design. The calcium content of the control meal was 3 mg/kg body mass, which was increased to 15 mg/kg body mass with calcium co-ingestion. Circulating concentrations of GIP 1–42 , GLP-1 and insulin were determined over a 180-min postprandial period, followed by 60 min of exercise. Visual analogue scales were used to determine subjective appetite sensations. Rates of energy expenditure and substrate (lipid and carbohydrate) oxidation were estimated using indirect calorimetry. Results Calcium co-ingestion resulted in a 47 % increase in GIP 1–42 , a 22 % increase in GLP-1 and a 19 % increase in insulin areas under the curve for the 120 min following consumption (all P  〈 0.05). Furthermore, appetite sensations were suppressed by calcium co-ingestion by 12 % ( P  = 0.034). No differences, however, were observed in substrate metabolism ( P  〉 0.05). Conclusion Ingestion of a high-calcium meal potentiates postprandial GIP 1–42 , GLP-1 and insulin concentrations in humans. Subjective appetite is also temporarily suppressed, although substrate metabolism is unaffected.

Description: Purpose The aim of this study is to evaluate the long-term influence of l -arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result. Methods A randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of l -arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used. Results We found that 6 months of l -arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P  〈 0.01) and zinc levels (Δ1.5 μmol/L, P  〈 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed ( R  = 0.80, P  〈 0.01). In the group of patients treated with l -arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted ( R  = −0.38, P  〈 0.05). Conclusions l -Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.

Description: Purpose To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism. Methods Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period. Results Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l , p  = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm ( p  = 0.003, p  = 0.04 and p  = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms. Conclusion/interpretation Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.

Description: Background and aims Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine—a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis—is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. Methods Two-month-old male Balb/c mice were submitted to protein-energy malnutrition ( n  = 10) with a low-protein diet containing 2 % protein, whereas control mice ( n  = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 μg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. Results Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. Conclusions These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

Description: Purpose To determine the relative impact of three iso-caloric breakfast meals, of variable composition, on satiety, hunger and subsequent intake of energy. Methods In a three-way, crossover design, 30 healthy men (age of 21.7 ± 1.2 years; BMI, 23.1 ± 2.7 kg/m 2 ) were randomised to one of three test breakfasts, on three separate occasions, separated by 1 week. The breakfasts consisted of eggs on toast, cereal (cornflakes) with milk and toast, or a croissant and orange juice. Subjective ratings of satiety, hunger, fullness and desire to eat were recorded at 30-min intervals by electronic visual analogue scales (VAS). Energy intake was assessed by weighed food intake at an ad libitum lunch and evening meal. Results Participants showed increased satiety, less hunger and a lower desire to eat after the breakfast containing eggs relative to the cereal ( p  〈 0.02), and croissant-based meals ( p  〈 0.0001). The egg breakfast was also accompanied by a significantly lower intake of energy relative to the croissant- and cereal-based breakfasts at the buffet lunch and evening meal, respectively, 1,284 ± 464 (egg) versus 1,442 ± 426 kcal (croissant), p  = 0.03, 1,407 ± 379 (cereal) at lunch and 1,899 ± 729 (egg) versus 2,214 ± 620 kcal (cereal), p  = 0.02, 2,047 ± 712 (croissant) at evening meal. The breakfast meal with the greatest effect on satiety and subsequent intake of energy was distinct in having the highest protein and lowest carbohydrate content relative to the other two breakfasts. Conclusion These findings provide evidence to support the importance of food choice at breakfast as a means of increasing satiety in the morning and reducing energy intake at lunch.

Description: Purpose Plant sterol (PS)-enriched food products are known to reduce plasma cholesterol concentrations by inhibiting the absorption of dietary and biliary cholesterol. The physiological responses induced by food intake in the gastrointestinal tract are all important factors in determining the overall effect of PS. The aim of this study was therefore to assess the effect of timing of consumption of a plant sterol (PS)–containing yoghurt drink relative to meal ingestion on gastric emptying (GE) of the drink and gallbladder (GB) volume. Methods This is a randomized, single-centre, controlled study with crossover design in 12 healthy male volunteers. Three treatments were tested; a 100 mL PS yoghurt drink (labeled with 1,000 mg acetaminophen) was consumed 45 min prior to, during and 45 min after a solid meal. Plasma samples were taken, and gallbladder volumes were measured at baseline and at regular intervals during a 6-h study period. Results When consumed before the consumption of a meal, the yoghurt drink exhibited fast GE. The solid meal intake caused a significant contraction of the gallbladder. Consumption of the PS drink before the meal had no significant effect on GB volume as compared to baseline and compared to during and after meal consumption. Conclusions The PS-containing drink, which empties fast from the stomach, does not sufficiently trigger gallbladder contraction without co-ingestion of a solid meal and in consequence does not induce the necessary physiological changes needed to allow PS to exhibit their effect on inhibiting cholesterol absorption.

Description: Purpose Influenza viruses infect airway epithelial cells, causing respiratory distress. Immune defense is maintained by chemokine/cytokine secretions from airway epithelial cells. While moderate inflammatory response protects from ill effects, hyper-inflammatory response promotes the pathogenesis. High circulating levels of vitamin D are known to mitigate effects of infectious diseases, including respiratory infectious diseases. The question whether and how vitamin D treatment pre-/post-viral exposure modulates inflammatory response is not clear. The present study was undertaken to understand autophagy/apoptosis balance and chemokine/cytokine response to influenza A (H1N1) infection by pre- and post-1, 25-dihydroxyvitamin D3 (1,25[OH]2 D3)[calcitriol] treatment of human lung A549 epithelial cells. Methods Influenza A (H1N1) virus was propagated in A549 cell line, titrated using hemagglutination assay, and was used to assess effect of calcitriol. After confirming that 100 nM of calcitriol fails to clear virus, A549 cells were either pre-treated (16 h) with 100 nM or post-treated with 30 nM of 1,25[OH]2 D3 of virus inoculation (1 h). Cells after incubation at 37 °C under 5 % CO2 for 48 h were collected and subjected to RNA and protein extraction. Measurements of viability, influenza M protein, and molecular parameters of cell death and inflammatory response were performed. Results We report that treatment of these cells with 100/30 nM of 1,25[OH]2 D3 prior to/or post-H1N1 exposure does not affect viral clearance but significantly reduces autophagy and restores increased apoptosis seen on H1N1 infection back to its constitutive level. However, it significantly decreases the levels of H1N1-induced TNF-α (tumor necrosis factor-alpha), IFN-β (interferon-beta), and IFN-stimulated gene-15 (ISG15). 1,25[OH]2 D3 treatment prior to/or post-H1N1 infection significantly down-regulates IL-8 as well as IL-6 RNA levels. These results demonstrate that calcitriol treatment suppresses the H1N1-induced transcription of the chemokines RANTES and IL-8 in epithelial cells. Conclusion The findings provide support for the initiation of vitamin D supplementation program to VDD populations in reducing the severity of influenza.

Description: Purpose It is relatively unknown how different dietary components, in partnership, regulate gene expression linked to colon pathology. It has been suggested that the combination of various bioactive components present in a plant-based diet is crucial for their potential anticancer activities. This study employed a combinatorial chemopreventive strategy to investigate the impact of selenium and/or isothiocyanates on DNA methylation processes in colorectal carcinoma cell lines. Methods To gain insights into the epigenetic-mediated changes in gene expression in response to these dietary constituents cultured Caco-2 and HCT116 cells were exposed for up to 12 days to different concentrations of selenium methylselenocysteine and selenite (ranging from 0.2 to 5 μM) either alone or in combination with sulforaphane and iberin (ranging from 6 to 8 μM), and changes to gene-specific ( p16 INK4A and ESR1 ), global (LINE-1) methylation and DNMT expression were quantified using real-time PCR-based assays. Results No effects on the methylation of CpG islands in ESR1 , p16 INK4A or of LINE-1, a marker of global genomic methylation, were observed after exposure of Caco-2 and HCT116 cells to selenium or isothiocyanates. Only transient changes in DNMT mRNA expression, which occurred mostly in the treatment groups containing isothiocyanates, were observed, and these occurred only for specific DNMT transcripts and did not lead to the modification of the aberrant methylation status present in these cells. Conclusion These data suggest that treatment for colon cancer cells with selenium and/or isothiocyanates, either individually or in combination does not impact abnormal methylation patterns of key genes involved in the complex multistep process of colon carcinogenesis in vitro.