ALBERT

Description: Purpose Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria might be an inflammation trigger in adipose tissue. It has recently been proposed that there is a link between adipose tissue distribution and blood LPS. However, the number of studies on this topic is scarce, and further investigation in humans is required. In this study, we explored the association between plasma LPS concentrations and body fat distribution, as well as the biochemical parameters that may indicate the presence of metabolic disorders. Methods Sixty-seven young adult men with body mass index of 26–35 kg/m 2 were evaluated. Anthropometry, body composition and body fat distribution, blood pressure, energy expenditure, physical activity level, dietary intake, and biochemical parameters were assessed. Results Men with median plasma LPS ≥ 0.9 EU/mL presented higher sagittal abdominal diameter, trunk fat percentage, and android fat percentage, and mass, insulin and alanine aminotransferase concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell dysfunction (HOMA-B) than those with lower plasma LPS. LPS correlated positively with the trunk fat percentage, and android fat percentage, and mass, insulin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations, as well as HOMA-IR and HOMA-B. Conclusion Our results suggest that a higher plasma LPS concentration is associated with a less favorable phenotype as characterized by higher central adiposity, higher values of HOMA-IR, and beta cell function impairment in overweight/obese men.

Description: Purpose The aim of this study was to evaluate and compare the musculoskeletal effects induced by ovariectomy-related fat mass deposition against the musculoskeletal effects caused by a high-fat diet. Methods A group of adult female rats was ovariectomized and fed a control diet. Two additional groups were sham-operated and fed a control or a high-fat diet for 19 weeks. Distal femur and serum bone parameters were measured to assess bone metabolism. Muscle protein metabolism, mitochondrial markers and triglyceride content were evaluated in tibialis anterior . Triglyceride content was evaluated in liver. Circulating inflammatory and metabolic markers were determined. Results The high-fat diet and ovariectomy led to similar increases in fat mass (+36.6–56.7 %; p  〈 0.05) but had different impacts on bone and muscle tissues and inflammatory markers. Consumption of the high-fat diet led to decreased bone formation (−38.4 %; p  〈 0.05), impaired muscle mitochondrial metabolism, muscle lipotoxicity and a 20.9 % increase in tibialis anterior protein synthesis rate ( p  〈 0.05). Ovariectomy was associated with higher bone turnover as bone formation increased +72.7 % ( p  〈 0.05) and bone resorption increased +76.4 % ( p  〈 0.05), leading to bone loss, a 17.9 % decrease in muscle protein synthesis rate ( p  〈 0.05) and liver lipotoxicity. Conclusions In female rats, high-fat diet and ovariectomy triggered similar gains in fat mass but had different impacts on bone and muscle metabolism. The ovariectomy-induced mechanisms affecting the musculoskeletal system are mainly caused by estrogen depletion, which surpasses the potential-independent effect of adiposity.

Description: In his offered opinion piece, (Dietary glycaemic load and cognitive performance in elderly subjects) Dr. Kawada comments upon the statistical analysis and suggests that the conclusions of the study should be interpreted with caution. Having closely examined these comments, we believe that they are over-stated and we draw different conclusions. At first viewing, the statistical arguments put forward by Dr. Kawada look complicated, but one may summarize that he believes the analysis lacked statistical power. This argument is directed towards two sets of regression analyses, a Poisson analysis on which one of the messages of the paper hinges, and a second logistic analysis that was acknowledged as statistically underpowered in our publication. No statistical argument is provided as to why the Poisson regression model is underpowered; the critique contains no new scientific content but relies on a technical re-iteration of the limitations of the study (that were highlighted in the original manuscript) combined with quasi philosophical arguments on data set size and the need for biochemical markers in observational dietary studies.

Description: Purpose Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response. We aimed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody (TPO-Ab) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population. Methods Samples and data were from a secondary analysis of Selenium in PRegnancy INTervention (SPRINT), a double-blind, randomized, placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation. Women were randomized to receive 60 µg/day selenium or placebo until delivery. Serum thyroid peroxidase antibodies (TPO-Ab), thyrotropin (TSH) and free thyroxine (FT4) were measured at 12, 20 and 35 weeks and thyroglobulin antibodies (Tg-Ab) at 12 weeks. Results 93.5 % of participants completed the study. Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy. In women who were either TPO-Ab or Tg-Ab negative at baseline (Thy-Ab −ve ), TSH increased and FT4 decreased significantly throughout gestation ( P  〈 0.001), with no difference between treatment groups. In women who were Thy-Ab +ve at baseline, TSH tended to decrease and was lower than placebo at 35 weeks ( P  = 0.050). FT4 fell more on Se than placebo supplementation and was significantly lower at 35 weeks ( P  = 0.029). Conclusions Low-dose selenium supplementation in pregnant women with mild-to-moderate deficiency had no effect on TPO-Ab concentration, but tended to change thyroid function in Thy-Ab +ve women.

Description: Purpose Currently, obesity has become a worldwide health problem. Adipocyte differentiation is closely associated with the onset of obesity. Our previous studies suggested that persimmon tannin might be a potent anti-adipogenic dietary bioactive compound. However, the mechanism of persimmon tannin on adipocyte differentiation is still unknown. The purpose of this study was to investigate the effect of persimmon tannin on adipogenic differentiation in 3T3-L1 preadipocytes and the underlying mechanisms. Methods Adipogenic differentiation was induced by cocktail in the presence or absence of persimmon tannin. Intracellular lipid accumulation was determined by Oil red O staining and enzymatic colorimetric methods. Gene expression and protein levels were measured by real time RT-PCR and Western blot. Results Persimmon tannin inhibited intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation. Persimmon tannin suppressed the expression of C/EBPα and peroxisome proliferator-activated receptor-γ (PPARγ), significantly. Furthermore, genes related to lipogenesis, such as sterol regulatory element-binding protein 1, were down-regulated by persimmon tannin. In addition, adipocyte fatty acid binding protein (aP2), which is a target gene of PPARγ, was suppressed by persimmon tannin notably. Correspondingly, the expression of miR-27a and miR-27b were up-regulated by persimmon tannin from Day 2 to Day 8 significantly. Conclusion Persimmon tannin inhibited adipocyte differentiation through regulation of PPARγ, C/EBPα and miR-27 in early stage of adipogenesis.

Description: Purpose Evidence suggests that dietary patterns compatible with the traditional Mediterranean diet (MD) may protect against cognitive decline. We prospectively assessed whether adherence to MD in the Mediterranean country of Greece is inversely associated with cognitive decline in the elderly and whether any particular MD component may play a key role. Methods Elderly men and women ( N  = 401) residing in the greater Athens area had dietary variables ascertained in 1994–1999. Adherence to MD was represented by the MD score [MDS, 0–3 (low), 4–5 (intermediate), 6–9 (high)]. The mini-mental state examination (MMSE) was administered by trained professionals to individuals aged 65 years or older in 2004–2006 (first assessment) and re-administered in 2011–2012 (second assessment). MMSE change (cMMSE) was categorized as: improved/unchanged (cMMSE ≥ 0), mildly lower (cMMSE −1 to −4) or substantially lower (cMMSE ≤ −5). Associations were evaluated through multinomial logistic regression. Results Decline in MMSE performance was inversely associated with adherence to MD. For mild versus no decline, odds ratio (OR) comparing high to low MD adherence was 0.46 [95 % confidence interval (CI) 0.25–0.87, p  = 0.012]. For substantial versus no decline, OR comparing high to low MD adherence was 0.34 (95 % CI 0.13–0.89, p  = 0.025). Among the nine MDS components, only vegetable consumption exhibited a significant inverse association with cognitive decline. Conclusions Closer adherence to the traditional MD is highly likely to protect against cognitive decline in this elderly Mediterranean population. Higher vegetable consumption appears to play a key role, possibly in synergy with additional components of the diet.

Description: Purpose Inhibitors of intestinal alpha-glucosidases are used therapeutically to treat type 2 diabetes mellitus. Bacteria such as Actinoplanes sp. naturally produce potent alpha-glucosidase inhibitor compounds, including the most widely available drug acarbose. It is not known whether lactic acid bacteria (LAB) colonising the human gut possess inhibitory potential against glucosidases. Hence, the study was undertaken to screen LABs having inherent alpha- and beta-glucosidase inhibitory potential. Methods This study isolated, screened, identified and extracted Lactobacillus strains (Lb1–15) from human infant faecal samples determining their inhibitory activity against intestinal maltase, sucrase, lactase and amylase. Lactobacillus reference strains (Ref1–7), a Gram positive control (Ctrl1) and two Gram negative controls (Ctrl2–3), were also analysed to compare activity. Results Faecal isolates were identified by DNA sequencing, with the majority identified as unique strains of Lactobacillus plantarum. Some strains ( L. plantarum , L. fermentum , L. casei and L . rhamnosus ) had potent and broad spectrum inhibitory activities (up to 89 %; p  〈 0.001; 500 mg/ml wet weight) comparable to acarbose (up to 88 %; p  〈 0.001; 30 mg/ml). Inhibitory activity was concentration-dependent and was freely available in the supernatant, and was not present in other bacterial genera ( Bifidobacterium bifidum and Escherichia coli or Salmonella typhimurium ). Interestingly, the potency and spectrum of inhibitory activity across strains of a single species ( L. plantarum ) differed substantially. Some Lactobacillus extracts had broader spectrum activities than acarbose, effectively inhibiting beta-glucosidase activity (lactase) as well as alpha-glucosidase activities (maltase, sucrase and amylase). Anti-diabetic potential was indicated by the fact that oral gavage with a L. rhamnosus extract (1 g/kg) was able to reduce glucose excursions (Area under curve; 22 %; p  〈 0.05) in rats during a carbohydrate challenge (starch; 2 g/kg). Conclusion These results definitively demonstrate that Lactobacillus strains present in the human gut have alpha- and beta-glucosidase inhibitory activities and can reduce blood glucose responses in vivo. Although the potential use of LAB such as Lactobacillus as a dietary supplement, medicinal food or biotherapeutic for diabetes is uncertain, such an approach might offer advantages over drug therapies in terms of broader spectrum activities and fewer unpleasant side effects. Further characterisation of this bioactivity is warranted, and chronic studies should be undertaken in appropriate animal models or diabetic subjects.

Description: Purpose Excessive fructose intake coincides with the growing rate of obesity and metabolic syndrome, with women being more prone to these disorders than men. Findings that detrimental effects of fructose might be mediated by glucocorticoid regeneration in adipose tissue only indirectly implicated glucocorticoid receptor (GR) in the phenomenon. The aim of the present study was to elucidate whether fructose overconsumption induces derangements in GR expression and function that might be associated with fructose-induced adiposity in females. Methods We examined effects of fructose-enriched diet on GR expression and function in visceral adipose tissue of female rats. Additionally, we analyzed the expression of genes involved in glucocorticoid prereceptor metabolism [11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase], lipolysis (hormone-sensitive lipase) and lipogenesis (sterol regulatory element binding protein 1 and peroxisomal proliferator-activated receptor γ). Results Fructose-fed rats had elevated energy intake that resulted in visceral adiposity, as indicated by increased visceral adipose tissue mass and its share in the whole-body weight. GR hormone binding capacity and affinity, as well as the expression of GR gene at both mRNA and protein levels were reduced in visceral adipose tissue of the rats on fructose diet. The glucocorticoid prereceptor metabolism was stimulated, as evidenced by elevated tissue corticosterone, while the key regulators of lipolysis and lipogenesis remained unaffected by fructose diet. Conclusions The results suggest that the 11βHSD1-mediated elevation of intracellular corticosterone may induce GR downregulation, which may be associated with failure of GR to stimulate lipolysis in fructose-fed female rats.

Description: Purpose Malnutrition increases the risk of developing alcohol-related complications. The aim of this study was to describe nutrient intake, nutritional status and nutrition-related complications in a Danish population of outpatients with alcohol dependency. Methods This was a cross-sectional study with a 6-month follow-up enrolling persons with alcohol dependency ( n  = 80) admitted to a hospital-based outpatient clinic. Body mass index, the waist-to-hip ratio and handgrip strength (HGS) were measured, a 7-day food diary was collected, and biochemical testing was conducted. Dual-energy X-ray absorptiometry was performed to determine body composition and bone mineral density (BMD). Results In total, 64 % of the patients with alcohol dependency had vitamin D insufficiency (25-OH-vit D 〈50 nmol/l). Compared with surveys of the general population, the patients with alcohol dependency had lower energy intake ( p  = 0.008), s-zinc levels ( p  〈 0.001), s-magnesium levels ( p  = 0.02), Z -scores for BMD (lumbar spine, p  = 0.03; total hip, p  = 0.009) and HGS ( p  〈 0.001). Osteopenia was observed in 52 % of individuals, and overt osteoporosis was noted in 7 %. Comparing baseline data with data from the follow-up ( n  = 30), we found a decrease in s-CRP ( p  = 0.002) and s-alanine amino transferase ( p  = 0.01) levels and an increase in s-parathyroid hormone levels ( p  = 0.02). Conclusions Patients with alcohol dependency have an altered nutritional status and risk of complications, as evidenced by osteopenia/osteoporosis and reduced muscle strength. Treatment at an outpatient clinic improved the variables related to liver function, but no change was observed in nutritional status over time. These findings suggest that specific screening and targeted treatment regimens for nutritional deficits could be beneficial.

Description: Purpose Aronia melanocarpa has an extremely high content of procyanidins and anthocyanins. The multidirectional benefits of consumption of these berries are widely reported. Although numerous studies confirmed the influence of polyphenols on various stages of hemostasis, the exact mechanism of this phenomenon is not understood. The aim of our study was to evaluate the in vitro effect of A. melanocarpa extract on various parameters of hemostasis. Methods Adenosine 5′-diphosphate (ADP)-induced aggregation was measured with turbidimetric method. Spontaneous and ADP-activated platelet adhesion were investigated using a colorimetric method. The global assay of coagulation and fibrinolysis was performed with the use of optical clotting and lysis (CL) test. Thrombin (0.5 IU/mL) and tissue plasminogen activator (60 ng/mL) were used to obtain a CL curve. The activity of thrombin and plasmin was determined by means of chromogenic substrate (S-2238, S-2251) Results The aronia extract contributed to the reduction in spontaneous and ADP-activated platelet adhesion. A significant increase in overall potential of CL as well as significant changes in key parameters of these processes ( T t —thrombin time, F vo —initial plasma clotting velocity, and L max —maximum lysis) was reported. Chokeberry extract significantly inhibited the amidolytic activity of thrombin and plasmin. Conclusion Our in vitro findings indicate a complex mechanism of influence of chokeberry polyphenols on platelet activity and the overall potential of CL. We confirmed that chokeberry inhibits the amidolytic activity of thrombin. It was demonstrated for the first time that chokeberry polyphenols inhibit the amidolytic activity of another serine protease, i.e., plasmin, which is the main fibrinolytic enzyme. Furthermore, our research points out a significant contribution of other plasma components and fibrinogen in the modulation of hemostasis by polyphenols.

Description: Purpose Meta-analyses have suggested an effect of MTHFR C677T genotype (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease (CVD) in populations with low population dietary folate. The aim was to examine the association and effect modification by serum folate and vitamin B12 levels between MTHFR and CVD-related outcomes in a general population with no mandatory folic acid fortification policy. Methods The study population included 13,748 adults retrieved from pooling of four population-based studies conducted in Denmark. MTHFR genotype, serum folate (measured in approximately 9,356 individuals), and serum vitamin B12 (9,215 individuals), hypertension, and dyslipidemia were measured at baseline, and participants were followed for a mean of 10.5–11.7 years in central registries for diagnoses of stroke (623 incidents), ischaemic heart disease (IHD) (835 incidents), and all-cause mortality (1,272 incidents). Results The MTHFR genotype (TT vs. CC/CT) was not associated with hypertension [OR (95 % CI) 1.09 (0.95–1.25)], dyslipidemia [OR (95 % CI) 0.97 (0.84–1.11)], stroke [HR (95 % CI) 0.92 (0.69–1.23)], and all-cause mortality [HR (95 % CI) 0.94 (0.77–1.14)], either overall, or in participants with low serum folate or B12 status ( P values for interactions 0.15–0.94). Individuals with the MTHFR TT genotype had a higher risk of IHD (HR (95 % CI) 1.38 (1.11–1.71)), but this association was not modified by folate status ( P value for interaction 0.45). Conclusions Our results do not support a causal relationship between homocysteine and CVD. However, we cannot exclude a direct causal effect of MTHFR C677T genotype on IHD.

Description: Objectives To study the association between the intake of fruit and vegetables and risk of esophageal adenocarcinoma (EAC), we summarized the evidence from observational studies in categorical and linear dose–response meta-analyses. Methods Eligible studies published up to June 2013 were retrieved via computerized searches of MEDLINE and EMBASE. Random-effects models were used to calculate summary relative risks (SRRs) and the corresponding 95 % confidence intervals (CIs). Between-study heterogeneity was assessed using the Cochran’s Q and I 2 statistics. Results A total of 12 studies involving 1,572 cases of EAC were included in this meta-analysis. Based on the highest versus lowest analysis, inverse associations were observed between intakes of vegetable (SRRs = 0.76, 95 % CIs 0.59–0.96; P heterogeneity  = 0.098, I 2 40.4 %; n  = 9 studies), intakes of fruit (SRRs = 0.73, 95 % CIs, 0.55–0.98; P heterogeneity  = 0.03, I 2  = 52.9 %; n  = 9 studies), and intakes of total vegetables and fruit combined (SRRs = 0.68, 95 % CI 0.49–0.93; P heterogeneity  = 0.162, I 2  = 38.9 %; n  = 5 studies). Similar results were also observed in a linear dose–response analysis. Conclusion These data support the hypothesis that intakes of vegetables and fruit may significantly reduce the risk of EAC. Further investigation with prospective designs, validated questionnaires, and good control of important confounders is warranted.

Description: Purpose Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. Method We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study ( n  = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. Results There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp ( P  〈 0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate ( P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort ( P  = 0.015). Conclusions High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

Description: Purpose Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults. Methods A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers. Results GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30–35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group ( P  〈 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group ( P  〈 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased 〉twofold in the high-dose group versus placebo ( P  〈 0.05) at 3 months. Conclusions These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.

Description: Purpose Poultry intake has been inconsistently associated with incidence or mortality of colorectal cancer (CRC) in epidemiologic studies. The purpose of this study was to assess their relationships by performing a dose–response meta-analysis. Methods We conducted a search of PubMed database between January 1966 and July 2013 for prospective studies that reported relative risks (RRs) with 95 % confidence interval (CIs) of CRC for at least three categories of poultry intake. Dose–response relationships were examined with the generalized least-squares trend estimation. Study-specific results were pooled with a random-effects model. Subgroup, sensitivity, and meta-regression analyses were also conducted to explore heterogeneity. Results Sixteen studies on poultry intake and CRC incidence, and four studies regarding poultry intake and CRC mortality were identified. These studies involved a total of 13,949 incident CRC cases and 983 CRC deaths. The RRs of CRC for higher compared with lower intake of poultry were reported in these studies, and the reported levels of poultry intake varied substantially. Results of the dose–response meta-analysis conferred a RR of 0.89 (95 % CI 0.81–0.97) for an increase in poultry intake of 50 g/day. The results were not sensitive to any individual studies and were similar for colon and rectal cancer. Poultry intake was not associated with CRC mortality (RR for 50 g/day = 0.97, 95 % CI 0.79–1.20). Conclusions This meta-analysis indicates that poultry intake may be moderately associated with reduced incidence of CRC.

Description: Purpose High glycemic load (GL) has been associated with excess stroke risk. Data suggest a different role of diet in the etiology of ischemic and hemorrhagic stroke. Methods We analyzed data from 19,824 participants of the Greek cohort of the population-based European Prospective Investigation into Cancer and nutrition (EPIC), who were free of cardiovascular diseases, cancer, and diabetes at baseline and had not developed diabetes. Diet was assessed at enrollment through a validated, interviewer-administered semi-quantitative food frequency questionnaire. The average daily GL was derived using standard tables. We also conducted a meta-analysis on GL and stroke (overall, ischemic and hemorrhagic), using random-effects models. Results In the Greek EPIC cohort, 304 incident stroke cases were identified (67 ischemic, 49 hemorrhagic). Using Cox proportional hazards regression models adjusted for potential confounders, the hazard ratios for the highest versus the lowest GL tertiles were 1.07 [95 % confidence interval (CI) 0.74–1.54] for overall stroke, 1.55 (95 % CI 0.72–3.36) for ischemic and 0.48 (95 % CI 0.18–1.25) for hemorrhagic stroke ( p -heterogeneity 〈0.01). The meta-analysis, including a total of 3,088 incident cases and 247 deaths from stroke (1,469 cases and 126 deaths ischemic; 576 cases and 94 deaths hemorrhagic), estimated pooled relative risks for the highest versus the lowest GL levels of 1.23 (95 % CI 1.07–1.41) for overall, 1.35 (95 % CI 1.06–1.72) for ischemic, and 1.09 (95 % CI 0.81–1.47) for hemorrhagic stroke ( p -heterogeneity = 0.275). Conclusions This study indicates that GL is an important determinant of the more common ischemic—though not of the hemorrhagic—stroke.

Description: Background During fetal development, docosahexaenoic (DHA) and arachidonic acid (ARA) are particularly enriched in brain phospholipids. After preterm delivery, fetal enrichment of DHA and ARA via placental transfer is replaced by enteral and parenteral nutrition, which is rich in linoleic acid (LA) instead. Specific DHA and ARA enrichment of lipoproteins is reflected by plasma phosphatidylcholine (PC) species, whereas plasma phosphatidylethanolamine (PE) composition reflects hepatic stores. Objective We profiled PC and PE species in preterm infant plasma, compared with cord and maternal blood, to assess whether current feeding practice meets fetal conditions in these patients. Design Preterm infant plasma ( N  = 171, 23–35 w postmenstrual age (PMA), postnatal day 1–103), cord plasma ( N  = 194) and maternal serum ( N  = 121) (both 24–41 w PMA) were collected. After lipid extraction, PC and PE molecular species were analyzed using tandem mass spectrometry. Results Phospholipid concentrations were higher in preterm infant than in cord plasma after correction for PMA. This was mainly due to postnatal increases in LA-containing PC and PE, resulting in decreased fractions of their DHA- and ARA-containing counterparts. These changes in preterm infant plasma phospholipids occurred during the time of transition to full enteral feeds (day 0–10 after delivery). Thereafter, the fraction of ARA-containing phospholipids further decreased, whereas that of DHA slowly reincreased but remained at a level 50 % of that of PMA-matched cord blood. Conclusions The postnatal increase in LA–PC in preterm infant plasma results in decreased fractions of DHA–PC and ARA–PC. These changes are also reflected by PE molecular composition as an indicator of altered hepatic fatty acid homeostasis. They are presumably caused by inadequately high LA, and low ARA and DHA supply, at a stage of development when ARA–PC and DHA–PC should be high, probably reducing the availability of DHA and ARA to the developing brain and contributing to impaired neurodevelopment of preterm infants.

Description: Objective Impaired insulin sensitivity (SI) and β-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, β-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D. Research design and methods Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the β-cell function were measured as well. Results The SI was significantly improved. At the same time, the static insulin responsivity index (Φ s ) was significantly higher after the treatment ( p  = 0.003). On the other hand, the dynamic insulin responsivity index (Φ d ) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment ( p  = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φ d after GaCr treatment. Conclusions In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φ s ) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φ s which indicated that the improvement of SI and Φ s might involve mechanisms other than lower inflammatory effect.

Description: Background Polyphenols are thought to play important roles in human nutrition and health but these health effects are dependent on their bioavailability. This study is one of a series with the aim of determining possible effects of food matrices on caffeoylquinic acid (CQA) bioavailability using ileostomy volunteers. Methods After a CQA-free diet, ileostomists consumed coffee (746 μmol total CQA), and CQAs in excreted ileal fluid were subsequently identified and quantified with HPLC–diode array detection and HPLC-ESI-MS/MS. In our previous studies, other food sources such as cloudy apple juice (CAJ) (358 μmol CQA) and apple smoothie (AS) (335 μmol CQA) were investigated with the same model. Results Interesterification of CQA from both apple matrices was observed during gastrointestinal passage, whereas CQA consumed in coffee was not influenced by interesterification reactions. In total, 74.3, 22.4, and 23.8 % of the CQA from CAJ, AS, and coffee, respectively, were absorbed or degraded. Conclusion Our results show that variations in food matrices and variations in phenolic composition have a major influence on intestinal bioavailability and interesterification of the investigated subclass of polyphenols, the CQAs.

Description: Purpose The aim of the study was to investigate how a diet high in dietary fiber, with several fiber sources included, modulates glucose and lipid metabolism and the inflammatory response in humans. Methods Subjects ( n  = 25) aged 58.6 (1.1) years (mean and SD) with a BMI of 26.6 (0.5) kg/m 2 and a total cholesterol (TC) of 5.8 (0.1) mmol/L (mean and SEM) were given a high fiber (HF) and low fiber (LF) diet, in a randomized controlled 5-week crossover intervention, separated by a 3-week washout. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products; one bread roll, one ready meal, and two beverages consumed daily. Equivalent food products, without added fibers, were provided in the LF diet. Results Total dietary fiber intake was 48.0 g and 30.2 g per day for the HF and LF diet, respectively. Significant reduction in C-reactive protein (CRP) was observed between the diets ( P  = 0.017) and a significant reduction in fibrinogen within the HF diet ( P  = 0.044). There were no significant effects in other measured circulating cytokines or in glucose, insulin, and lipid levels. Conclusions Our study suggests that a 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber might reduce the low-grade inflammatory response measured as CRP which could, together with reduced fibrinogen, help to prevent the risk of cardiovascular disease.

Description: Purpose To investigate the protective mechanisms of an 85 % pure extract of (−) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD). Methods Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses. Results Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats. Conclusions Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.

Description: Purpose Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI − ) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, possible mechanisms contributing to the athero-protective effect of soy protein remain unknown. Therefore, we investigated whether and how SPI − diet inhibits inflammatory responses associated with atherosclerosis. Methods Apolipoprotein E knockout (apoE−/−) mice (5-week) were fed CAS or SPI − diet for 1 or 5 week to determine LPS- and hyperlipidemia-induced acute and chronic inflammatory responses, respectively. Expression of NF-κB-dependent inflammation mediators such as VCAM-1, TNF-α, and MCP-1 were determined in aorta and liver. NF-κB, MAP kinase, and AKT activation was determined to address mechanisms contributing to the anti-inflammatory properties of soy protein/peptides. Results Isoflavone-free soy protein diet significantly reduced LPS-induced VCAM-1 mRNA and protein expression in aorta compared to CAS-fed mice. Reduced VCAM-1 expression in SPI − -fed mice also paralleled attenuated monocyte adhesion to vascular endothelium, a critical and primary processes during inflammation. Notably, VCAM-1 mRNA and protein expression in lesion-prone aortic arch was significantly reduced in apoE−/− mice fed SPI − for 5 weeks compared with CAS-fed mice. Moreover, dietary SPI − potently inhibited LPS-induced NF-κB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and MCP-1. Interestingly, SPI − inhibited NF-κB-dependent inflammatory responses by targeting I-κB phosphorylation and AKT activation with no effect on MAP kinase pathway. Of the five putative soy peptides, four of the soy peptides inhibited LPS-induced VCAM-1, IL-6, IL-8, and MCP-1 protein expression in human vascular endothelial cells in vitro. Conclusions Collectively, our findings suggest that anti-inflammatory properties of component(s) of soy protein/peptides may be a possible mechanism for the prevention of chronic inflammatory diseases such as atherosclerosis.

Description: Purpose Previous studies regarding the association between carrot intake and prostate cancer risk have reported inconsistent results. We conducted a meta-analysis to summarize evidence on this association and to quantify the potential dose–response relationship. Method A systematic literature search of papers published in August 2013 was conducted using PubMed, EMBASE, Scopus, Web of Science, the Cochrane register, and the Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles were screened. The summary risk estimates with 95 % confidence intervals (CIs) for the highest versus the lowest intake of carrots were calculated. A dose–response meta-analysis was also conducted for the studies reporting categorical risk estimates for a series of exposure levels. Results We found a significantly decreased risk of prostate cancer associated with the intake of carrots (odds ratio 0.82, 95 % CI 0.70–0.97). In addition, the dose–response meta-analysis indicated that for each serving per week, or 10 g per day increment of carrot intake, the risk estimate of prostate cancer was 0.95 (0.90–0.99) or 0.96 (0.94–0.99). There was no evidence of significant publication bias based on Begg’s funnel plot ( P  = 1.000) or Egger’s test ( P  = 0.804). Conclusion Carrot intake might be inversely associated with prostate cancer risk. Because of the limited number of cohort studies and substantial heterogeneity observed between studies in this meta-analysis, further well-designed prospective studies are warranted to confirm the findings from our study.

Description: Purpose Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. Methods The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. Results In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups ( p  = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 μmol/L (95 % CI 1.93–25.6, p  = 0.023) or 4.9 % (95 % CI 1.3–8.5 %, p  = 0.023) between the combined soy foods group and placebo group. Conclusions Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.

Description: Purpose Given the current prevalence of obesity, it is important to identify dietary factors that may aid in disease prevention. The objective of the present study was to evaluate the association between consumption of an energy-dense diet and established markers factors for chronic disease, including body weight and measures of body fatness. Methods Data from a nationally representative sample of 9,551 adults ≥18 years who participated in the 2005–2008 National Health and Nutrition Examination Survey were analyzed. The association between dietary energy density (ED, energy per weight of food, kcal/g) and markers for obesity [including body mass index (BMI) and waist circumference (WC)], insulin insensitivity [including fasting glucose, insulin and homeostasis assessment model for insulin resistance (HOMA-IR)], and markers for inflammation was examined. Results Dietary ED was positively associated with obesity in both men and women in multivariate models. Overall, obese adults had a significantly higher dietary ED than lean adults ( p  〈 0.0001). Current smokers had significantly higher ED than non-smokers (2.00 vs. 1.75, p  〈 0.01), and it was determined that smoking status modified the relationship between ED and weight status in women ( p interaction 0.03). In both sexes, there was a positive linear relationship between BMI and ED ( p trend 0.01 and 0.0002, respectively); a linear trend between WC and ED was also observed in women ( p trend 〈0.001) after adjusting for relevant cofactors. In women, ED was positively associated with HOMA-IR and fasting insulin; though, this relationship was not observed in men. No significant associations between ED and C-reactive protein were observed in either sex. Conclusion These findings support recent obesity and disease prevention recommendations to consume a diet low in ED.

Description: Purpose The New Nordic Diet (NND) has induced weight loss in a 26-week controlled intervention. We aim to investigate whether high compliance and satisfaction can be maintained after the active intervention is discontinued thereby maintaining the health effects. Methods After 26 weeks of intervention with NND or Average Danish Diet (ADD), 147 participants (mean age 43 years and mean BMI 29.1 kg/m 2 ) were followed for further 52 weeks. All participants were encouraged to follow NND but without further guidance. The study is registered with ClinicalTrials.gov, study id NCT01195610. Results One hundred and ten participants (75 %) completed the follow-up. Among participants previously randomised to NND (NND group), dietary compliance and satisfaction decreased from 4.3 to 3.0 and from 4.8 to 4.0, respectively (both p  〈 0.0001) (1–5 point scale). Among those originally randomised to ADD (ADD group), satisfaction with NND was significantly higher than with ADD during follow-up (3.3 vs. 2.5, p  = 0.026). Weight losses during intervention of −6.2 kg and −3.0 kg were followed by regains of 4.6 kg (SE 0.5) and 1.1 kg (SE 0.7) for the NND group and ADD group, respectively [adjusted difference; mean (95 % CI): 1.8 kg (0.1–3.4), p  = 0.041]. Across diet groups, every 1 score higher in compliance with NND was associated with 0.90 kg less body weight regain ( p  = 0.026) and those who increased physical activity regained 3.4 kg less compared to those who did not ( p  〈 0.0001). Conclusions NND provides higher satisfaction, and body weight regain is reduced with higher compliance with NND and increased physical activity.

Description: Purpose Currently, there is no consensus concerning the possible beneficial colonic and systemic effects of prebiotic-containing infant formula. This study assesses whether the feeding of a galactooligosaccharides (GOS)-containing infant formula (0.44 g/dl of GOS) and the subsequent feeding of a GOS-containing follow-on formula (0.50 g/dl of GOS) have a prebiotic effect on intestinal microbiota that helps to decrease infections and allergy manifestations in healthy infants during the first year of life. Methods A multicentre, randomised, double-blind and placebo-controlled trial was carried out on 365 healthy term infants enrolled before 8 weeks of age and randomly assigned to a formula with or without GOS, until 12 months of age. The incidence of infections and allergy manifestations, the antibiotics prescribed and faecal characteristics were recorded up to 12 months of age, while faecal samples were collected up to 4 months for the measurement of secretory immunoglobulin A, short-chain fatty acids and microbiota. Results A prebiotic effect on the faecal analysis was observed at 4 months of life. The GOS group showed a lower faecal pH ( P  = 0.019), a lower decreasing trend in secretory immunoglobulin A ( P  = 0.078), lower butyric acid concentration ( P  = 0.040) and an increase in Bifidobacterium counts ( P  = 0.010). Changes in faecal characteristics involved greater frequency ( P  〈 0.001) and softer consistency ( P  〈 0.05). The incidence of infections or allergic manifestations during the first year of life was similar in both groups, with no statistical differences ( P  〉 0.05). Conclusions The feeding of GOS-containing infant formula produced a definite prebiotic effect consisting of changes in faecal composition and microbiota, and in faecal consistency and the frequency of defaecation. No changes in the incidence of infection or allergic manifestation during the first year of life were observed.

Description: Purpose Breast-feeding (BF) versus formula-feeding (FF) may be a factor for the development and differentiation of T-cell subsets and cytokine production in infancy and childhood. We therefore investigated T-cell subpopulations and their cytokine production by flow cytometry as well as cytokine levels in serum samples in breast-fed versus formula-fed infants and children. Methods Heparinised blood was taken from 191 healthy infants and children. Peripheral blood mononuclear cells were stimulated with phorbol-mystriate-acetate and ionomycin in the presence of brefeldin. T-cell subsets and cytokines were determined by flow cytometry. Furthermore, serum concentrations of IFNγ and IL4 were measured using ELISA. An IFNγ/IL4 ratio was calculated to estimate the Th1/Th2 balance. Results Children who were formula-fed show higher numbers of memory T and T helper cells. After stimulation, the number of IFNγ-positive memory T-cells was increased up to the age of 6 years. Breast-fed infants show higher percentages of IL4-positive T helper cells. At ELISA determination, formula-fed children showed higher IFNγ levels than breast-fed children, while IL4 levels did not differ. The IFNγ/IL4 ratio (FACS and ELISA) was elevated in formula-fed infants and children. Conclusion This systematic analysis of cytokine profiles during childhood in dependency of BF allows a better understanding of immune maturation and demonstrates the influence of early feeding on immune function throughout childhood, even after cessation of BF. FF induces a shift towards Th1 cytokines in children. This may have an influence on the development of autoimmune disease in later life.

Description: Purpose Recent data suggest that chronic low-grade inflammation, a characteristic of obesity, is associated with altered tryptophan (Trp) and tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The present study assessed the effect of an extreme short-term diet on Trp breakdown and inflammatory biomarkers in overweight adults. Methods Thirty-eight overweight participants (16 women, 22 men; average body mass index: 29 kg/m 2 , mean age 52.8 years) were randomized into two diet groups: a very low kcal diet group (VLCD; Ø 600 kcal/day, n  = 21) and a low kcal diet group (LCD; Ø 1,200 kcal/day, n  = 17). Assays included the measurement of Trp, kynurenine (Kyn), and their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin, plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as biochemical and inflammatory markers at baseline and after 2 weeks of treatment. Results Weight loss diet lowered leptin levels in both groups by 46 %, although not reaching significance. Trp and Kyn decreased significantly by 21 and 16 % for VLCD and by 15 and 17 % for the LCD group, respectively. A significant reduction in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were not significantly altered during the study period. Leptin was significantly correlated with Trp breakdown before and after the intervention ( P  〈 0.02). Conclusions Since disturbed metabolism of Trp affects biosynthesis of serotonin and might be associated with increased susceptibility for mood disturbances and carbohydrate craving, strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms.

Description: Purpose Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice—independent of dietary vitC—are able to modulate their vitC homeostasis during high-fat (HF) feeding. Methods Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates. Results HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat ( P  〈 0.05). Hepatic de novo biosynthesis of vitC was upregulated ( P  〈 0.05) as measured by GLO capacity, and liver vitC was reduced ( P  〈 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT ( P  〈 0.05). Conclusion Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.

Description: Purpose To investigate whether breast-milk composition and microbiota differ in healthy mothers and mothers with celiac disease (CD) to ultimately contribute to identify additional factors determining CD risk. Methods Breast-milk samples from healthy mothers ( n  = 12) and mothers with CD ( n  = 12) were collected. Cytokines and secretory immunoglobulin A (sIgA) were analyzed by bead-arrays and flow cytometry and human milk oligosaccharides (HMOs) were assessed by capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection. Breast-milk microbiota composition was analyzed by conventional and quantitative real-time PCR. Result Breast milk from CD mothers showed significantly lower levels of interleukin (IL) 12p70 ( P  〈 0.042), transforming growth factor (TGF)-β1 ( P  〈 0.018) and sIgA ( P  〈 0.003) and almost significantly lower levels of interferon (IFN)-γ ( P  〈 0.058). Six mothers in each group belonged to the secretor Le(a−b+) type, one to the secretor Le(a−b−) type and five to the non-secretor Le(a+b−) type. CD mothers of non-secretor Le(a+b−) type showed increased Lacto- N -tetraose content ( P  〈 0.042) compared with healthy mothers. CD mothers’ milk showed reduced gene copy numbers of Bifidobacterium spp. ( P  〈 0.026) and B. fragilis group ( P  〈 0.044). Conclusion CD mothers’ breast milk is characterized by a reduced abundance of immunoprotective compounds (TGF-β1 and sIgA) and bifidobacteria. The reduction in these components could theoretically diminish the protective effects of breast-feeding on the child’s future risk of developing CD.

Description: Purpose Brain insulin resistance is related to both diabetes and Alzheimer’s disease. We investigated whether both chungkookjangs, soybeans fermented in a traditional method (TFC) and with Bacillus lichenifomis (SFC), can protect against cognitive dysfunction and glucose dysregulation in rats with Alzheimer’s disease and type 2 diabetes. Methods Partial pancreatectomy (Px) and ICV β-amyloid (25–35) infusion into the CA1 region were fed either control diet (AD–CON), 10 % cooked soybeans (CSB), 10 % TFC, or 10 % SFC in a high fat diet for 8 weeks. Px rats infused β-amyloid (35–25) as a normal-control group (Non-AD–CON). Results SFC increased isoflavonoid aglycones, DDMP soyasaponin βg, E soyasaponin Be and lysoposphatidylcholines in comparison to CSB. SFC markedly decreased its accumulation in β-amyloid deposition in AD rats and improved hippocampal insulin signaling (pAkt → pGSK → pTau) that exacerbated in AD–CON rats. AD rats markedly impaired cognitive function than Non-AD–CON rats as measured by a water maze and passive avoidance tests while the disturbance was prevented in an ascending order of CON 〈 CSB and TFC 〈 SFC. In comparison to Non-AD rats, AD–CON rats lowered whole body glucose infusion rates and increased hepatic glucose output at hyperinsulinemic state during euglycemic hyperinsulinemic clamp which SFC normalized in AD rats. Interestingly, insulin secretion, especially at the second phase during hyperglycemic clamp, was higher in AD–CON rats, compared to Non-AD rats while CSB, TFC, SFC lowered it in AD-rats. However, SFC restored β-cell mass in AD rats that reduced β-cell mass by increased β-cell apoptosis. Conclusions β-Amyloid accumulation in the hippocampus exacerbated insulin resistance and decreased β-cell mass and SFC prevented their exacerbation in AD diabetic rats.

Description: Purpose The aim of the study was to investigate the influence of foods enriched with vegetable oils varying in their n -3 polyunsaturated fatty acids profile on cardiovascular risk factors for hypertriglyceridemic subjects. Methods Fifty-nine hypertriglyceridemic subjects (triglycerides ≥ 1.5 mmol/L) were included in the randomized, double-blind, placebo-controlled, crossover study. The placebo group received sunflower oil [linoleic acid (LA) group; 10 g LA/day]. The intervention groups received linseed oil [α-linolenic acid (ALA) group; 7 g ALA/day], echium oil [stearidonic acid (SDA) group; 2 g SDA/day] or microalgae oil [docosahexaenoic acid (DHA) group; 2 g DHA/day] over 10 weeks. Blood samples were collected at baseline and at the end of each period. Results Total cholesterol (TC) and low-density-lipoprotein cholesterol decreased significantly in the LA and ALA groups (LA: P  ≤ 0.01, ALA: P  ≤ 0.05). No changes in blood lipids were observed in the SDA group. Significant increases in TC and high-density-lipoprotein cholesterol occurred in the DHA group ( P  ≤ 0.05). In the ALA and SDA groups, the content of eicosapentaenoic acid in erythrocyte lipids increased significantly ( P  ≤ 0.05) after 10 weeks (ALA group: 38 ± 37 %, SDA group: 73  ± 59 %). Conclusion Foods enriched with different vegetable oils rich in ALA or SDA are able to increase the n -3 long-chain polyunsaturated fatty acids content in erythrocyte lipids; echium oil is more potent in comparison with linseed oil. Blood lipids were beneficially modified through the consumption of food products enriched with sunflower, linseed and microalgae oils, whereas echium oil did not affect blood lipids. ClinicalTrials.gov: NCT01437930.

Description: Purpose To assess the effect of consuming a mid-morning almond snack (28 and 42 g) tested against a negative control of no almonds on acute satiety responses. Method On three test days, 32 healthy females consumed a standard breakfast followed by 0, 28 or 42 g of almonds as a mid-morning snack and then ad libitum meals at lunch and dinner. The effect of the almond snacks on satiety was assessed by measuring energy intake (kcal) at the two ad libitum meals and subjective appetite ratings (visual analogue scales) throughout the test days. Results Intake at lunch and dinner significantly decreased in a dose-dependent manner in response to the almond snacks. Overall, a similar amount of energy was consumed on all three test days indicating that participants compensated for the 173 and 259 kcals consumed as almonds on the 28 and 42 g test days, respectively. Subjective appetite ratings in the interval between the mid-morning snack and lunch were consistent with dose-dependent enhanced satiety following the almond snacks. However, in the interval between lunch and dinner, appetite ratings were not dependent on the mid-morning snack. Conclusion Almonds might be a healthy snack option since their acute satiating effects are likely to result in no net increase in energy consumed over a day.

Description: Purpose Regular consumption of extra virgin olive oil (EVOO) is associated with a low incidence of atherosclerotic diseases. The phenolic component contributes to the hypolipidemic action of EVOO, although the biochemical mechanisms leading this beneficial outcome are not fully understood. Since liver plays a pivotal role in the whole body lipid homeostasis, we investigated the short-term effects of EVOO extract, with a high phenol content (HPE), on lipid synthesis in primary rat hepatocytes. Refined olive oil extract, with a low phenol content, was used throughout this study as a control. Methods Olive oil phenols isolated with methanolic extractions were subsequently analyzed by high performance liquid chromatography, electrospray ionization tandem mass spectrometry, and gas chromatography mass spectrometry. Rat hepatocytes were obtained from collagenase perfusion of liver. A colorimetric assay was performed to exclude cytotoxicity of the extracts. Radioenzymatic methods were used in order to investigate hepatic lipid metabolism. Results HPE, dose- (0.1–50 μg/mL) and time-dependently (0.5–4 h) inhibited both lipogenesis and cholesterogenesis ( n  = 6, P  〈 0.05), as well as triglycerides synthesis ( n  = 5, P  〈 0.05). We showed that these effects are attributable to a short-term modulation by HPE of the key enzymes implicated in the abovementioned pathways ( n  = 5, P  〈 0.05). Conclusions The decrease in hepatic lipid synthesis may represent a potential mechanism underlying the hypolipidemic effect of EVOO phenols.

Description: Background Substantial increases in dietary sugar intake together with the increasing prevalence of obesity worldwide, as well as the parallels found between sugar overconsumption and drug abuse, have motivated research on the adverse effects of sugars on health and eating behaviour. Given that the gut–brain axis depends on multiple interactions between peripheral and central signals, and because these signals are interdependent, it is crucial to have a holistic view about dietary sugar effects on health. Methods Recent data on the effects of dietary sugars (i.e. sucrose, glucose, and fructose) at both peripheral and central levels and their interactions will be critically discussed in order to improve our understanding of the effects of sugars on health and diseases. This will contribute to the development of more efficient strategies for the prevention and treatment for obesity and associated co-morbidities. Results This review highlights opposing effects of glucose and fructose on metabolism and eating behaviour. Peripheral glucose and fructose sensing may influence eating behaviour by sweet-tasting mechanisms in the mouth and gut, and by glucose-sensing mechanisms in the gut. Glucose may impact brain reward regions and eating behaviour directly by crossing the blood–brain barrier, and indirectly by peripheral neural input and by oral and intestinal sweet taste/sugar-sensing mechanisms, whereas those promoted by fructose orally ingested seem to rely only on these indirect mechanisms. Conclusions Given the discrepancies between studies regarding the metabolic effects of sugars, more studies using physiological experimental conditions and in animal models closer to humans are needed. Additional studies directly comparing the effects of sucrose, glucose, and fructose should be performed to elucidate possible differences between these sugars on the reward circuitry.

Description: Purpose We examined whether consumption of total dairy and dairy subgroups was related to incident stroke and coronary heart disease (CHD) in a general older Dutch population. Methods The study involved 4,235 participants of the Rotterdam Study aged 55 and over who were free of cardiovascular disease (CVD) and diabetes at baseline (1990–1993). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) for the intake of total dairy and dairy subgroups in relation to incident CVD events. Results Median intake of total dairy was 397 g/day, which mainly comprised low-fat dairy products (median intake of 247 g/day). During a median follow-up time of 17.3 years, 564 strokes (182 fatal) and 567 CHD events (350 fatal) occurred. Total dairy, milk, low-fat dairy, and fermented dairy were not significantly related to incident stroke or fatal stroke ( p  〉 0.2 for upper vs. lower intake categories). High-fat dairy was significantly inversely related to fatal stroke (HR of 0.88 per 100 g/day; 95 % CI 0.79, 0.99), but not to incident stroke (HR of 0.96 per 100 g/day; 95 % CI 0.90, 1.02). Total dairy or dairy subgroups were not significantly related to incident CHD or fatal CHD (HRs between 0.98 and 1.05 per 100 g/day, all p  〉 0.35). Conclusions In this long-term follow-up study of older Dutch subjects, total dairy consumption or the intake of specific dairy products was not related to the occurrence of CVD events. The observed inverse association between high-fat dairy and fatal stroke warrants confirmation in other studies.

Description: Purpose The vitamin D system plays a role in metabolism regulation. 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) suppressed 3T3-L1 white adipocyte differentiation. Vitamin D receptor (VDR) knockout mice showed increased energy expenditure, whereas mice with adipose-specific VDR over-expression showed decreased energy expenditure. Brown adipose tissue (BAT), now known to be present in adult humans, functions in non-shivering thermogenesis by uncoupling ATP synthesis from respiration and plays an important role in energy expenditure. However, the effects of 1,25(OH) 2 D 3 /VDR on brown adipocyte differentiation and mitochondrial respiration have not been reported. Methods mRNA expression of VDR and the metabolizing enzymes 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1) were examined in BAT of mice models of obesity and during brown adipocyte differentiation. The effects of 1,25(OH) 2 D 3 and VDR over-expression on brown adipocyte differentiation and functional outcomes were evaluated. Results No significant changes in mRNA of VDR and CYP27B1 were noted in both diet-induced obese (DIO) and ob/ob mice, whereas uncoupling protein 1 mRNA was downregulated in BAT of ob/ob , but not DIO mice when compared to the controls. In contrast, mRNA of VDR, CYP24A1, and CYP27B1 were downregulated during brown adipocyte differentiation in vitro. 1,25(OH) 2 D 3 dose-dependently suppressed brown adipocyte differentiation, accompanied by suppressed isoproterenol-stimulated oxygen consumption rates (OCR), maximal OCR and OCR from proton leak. Consistently, over-expression of VDR also suppressed brown adipocyte differentiation. Further, both 1,25(OH) 2 D 3 and VDR over-expression suppressed PPARγ transactivation in brown preadipocytes. Conclusion Our results demonstrate the suppressive effects of 1,25(OH) 2 D 3 /VDR signaling on brown adipocyte differentiation and mitochondrial respiration. The role of 1,25(OH) 2 D 3 /VDR system in regulating BAT development and function in obesity warrant further investigation.

Description: Purpose A high dietary salt intake is a serious risk factor for the development of hypertension. Daily salt intake in most of the European countries substantially exceeds the current recommendations of salt intake. For Germany, so far, no valid biomarker-based data on current daily salt intake are available. Methods Data basis for this biomarker-based estimation of salt intake in the German population was the representative DEGS Study (German Health Interview and Examination Survey for Adults) conducted 2008–2011 in 18–79 old adults living in Germany. Daily salt intake was estimated from 6,962 sodium and creatinine measurements in spot urine samples. Results Median estimated daily salt intake of the 18–79 olds was 10.0 g in men and 8.4 g in women. More than 75 % of men and about 70 % of women exceeded the current recommendation of a maximum salt intake of 6 g/day. Fifty percentage of men and more than 35 % of the women had a daily salt intake 〉10 g. Conclusion Daily salt intake of the German population considerably exceeds the current recommendation to eat no more than 6 g salt per day. A general reduction of salt content in processed foods—which are currently the main source of salt intake—offers a promising and cost-effective potential for the improvement of all salt intake-dependent health outcomes in the population.

Description: Purpose Several nutrients act as phytoestrogens, being anti-adipogenic when consumed with a fat-rich diet. Their effect on a low-fat diet (LFD) background is unknown. We tested soy and genistein effects on adipose tissue in LFD-fed mice and genistein activity in the 3T3-L1 adipogenesis model. Methods C57BL/6 J male mice were fed an 8.5 % soy-supplemented LFD (SS-LFD) or a soy-free LFD (SF-LFD) for 147 days. Groups of 3-week-old (pubertal) and 6-week-old (adult) mice on the SF-LFD were also treated with 17ß-estradiol (E2, 5 µg/kg/day) ip or pure genistein (5 mg/kg/day) by gavage for 15 days. Body fat deposition and gene expression profiles were evaluated. E2 and genistein effects on ERα, ERβ and PPARγ transcriptional activities were characterized in ERα- or ERβ-transfected 3T3L1 cells during differentiation, by the use of reporter plasmids. Results The SS-LFD group increased fat mass compared with the SF-LFD group. Genistein alone increased while E2 decreased fat pads in the 15-day-treated mice. In visceral fat, genistein differentially regulated 13 metabolic pathways compared to E2. PPARγ-controlled genes were downregulated by E2, while they were upregulated by genistein. In 3T3-L1 cells, genistein activated ERβ-driven transcription, differentiation and lipid accumulation, while inhibited ERα-driven transcription, without effects on lipid accumulation. E2 activated both ERs only in preadipocytes. In differentiated untransfected cells, genistein inhibited PPARγ, while activated PPARγ in the presence of ERβ. Conclusions Soy and genistein at nutritional doses induce fat development in LFD-fed mice and adipogenesis in 3T3-L1 cells, with a mechanism that involves, at least in vitro, ERβ and is dependent on cell differentiation stage.

Description: Purpose The aim of this study was to evaluate whether daily consumption of coffee and tea was associated with components and prevalence of metabolic syndrome (MetS) in the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe cohort study. Methods A cross-sectional population-based survey including 8,821 adults (51.4 % female) was conducted in Krakow, Poland. Coffee and tea consumption was evaluated using food frequency questionnaires. MetS was defined according to the International Diabetes Federation definition. Linear and logistic regression models were performed to estimate odds ratios and confidence intervals. Results Among high coffee and tea consumers (3 or more cups/day), high prevalence of female gender, young age, medium–high educational and occupational level, high total energy intake, and smoking habit were found. High coffee drinkers had lower BMI, waist circumference, systolic and diastolic blood pressure, triglycerides, and higher HDL cholesterol than those drinking less than 1 cup/day. In contrast, high tea consumers had lower BMI, waist circumference, but not diastolic blood pressure, which was higher than low drinkers. After adjusting for potential confounding factors, both higher coffee and tea consumption were negatively associated with MetS (OR 0.75, 95 % CI 0.66, 0.86 and OR 0.79, 95 % CI 0.67, 0.92, respectively). Among specific components of MetS, high coffee consumption was negatively associated with waist circumference, hypertension, and triglycerides, whereas tea consumption with central obesity and fasting plasma glucose in women, but not in men. Conclusions Coffee and tea consumption was negatively associated with MetS and some of its components.

Description: Purpose Besides the adverse health effects of a low folate intake, the risks of high intakes of folic acid have moved into the focus. The aim of this study was to investigate the potential range of folate and folic acid intake of the German population under consideration of different fortification scenarios. Methods Food consumption data of 13,926 participants of the German National Nutrition Survey II (NVS II), collected with two 24-h recalls, were used to calculate the nutrient intake. The nutrient data are based on the German Nutrient Database (BLS), information from a market survey and analyses of multivitamin juices. The scenarios were modelled without, as well as with low and high fortification levels of folic acid. Results The median intake of dietary folate equivalents ranged from 191 µg/d (men) and 168 µg/d (women) without fortification to 425 µg/d (men) and 334 µg/d (women) in the highest fortification scenario. Thus, 12.4–68.2 % (men) and 5.9–56.1 % (women) met the 300 µg/d recommended by the nutrition societies of Germany, Austria and Switzerland. In the highest fortification scenario, 1.9 % (men) and 0.8 % (women) exceeded the tolerable upper intake level (UL) of 1,000 µg/d folic acid given by the European Food Safety Authority. For supplement users, this proportion was 5.2 and 5.4 %. Conclusions Only a high fortification of several foods leads to a marked increase of the proportion of population reaching the recommendation. Simultaneously, with a high fortification a higher proportion exceeds the UL, especially in combination with supplements.

Description: Purpose Thymoquinone (TQ), a bioactive constituent of Nigella sativa (Linn.) seed, which is commonly used as a spice in Asian food, has been reported to possess a wide range of biological effects. The present study evaluated the effect of TQ on high-fructose diet (HFD)-induced metabolic syndrome (MetS) in male Wistar rats. Methods MetS was induced by 60 % HFD over 42 days. TQ (25, 50 and 100 mg/kg, p.o. once daily) was administered along with HFD for 42 days. Pioglitazone (10 mg/kg, p.o. once daily) was used as a standard drug. Plasma glucose, triglycerides, total cholesterol and HDL-cholesterol were estimated on days 0 and 42. Change in blood pressure, oral glucose tolerance and insulin resistance were measured. Hepatic thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase levels were estimated as measures of hepatic oxidative stress. Hepatic mRNA of PPAR-α and PPAR-γ was also studied. Results TQ prevented the characteristic features of HFD-induced MetS, such as hyperglycaemia, hypertriglyceridemia, hypercholesterolaemia and elevated systolic blood pressure. TQ also prevented impaired glucose tolerance and insulin resistance. It also ameliorated HFD-induced increase in hepatic TBARS and depletion of SOD, catalase and GSH. TQ prevented reduction in hepatic mRNA of PPAR-α and PPAR-γ in HFD rats, and the effects were comparable to those of pioglitazone. Conclusions This study demonstrates protective effect of TQ against HFD-induced MetS on rats which might have been mediated via PPAR mechanism.

Description: Purpose The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20 % beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS. Methods Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20 % solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks. Results Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS. Conclusions Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.

Description: Purpose Tomato products are a dietary source of natural antioxidants, especially lycopene, which accumulates in the liver, where it exerts biological effects. Taking into consideration this fact, the aim of the present study was to ascertain the effect of tomato consumption on biomarkers and gene expression related to lipid metabolism in rats with induced steatosis. Methods Adult male Sprague–Dawley rats (8 weeks old) were randomly grouped ( n  = 6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high fat diet and water) and HL (high fat diet and tomato juice). After 7 weeks, rats were euthanized, and plasma, urine, feces and liver were sampled to analyze the biomarkers related to lipid metabolism, inflammation and oxidative stress. Results The H diet induced steatosis (grade II) in the HA and HL groups, which was confirmed by the levels of alanine aminotransferase and aspartate aminotransferase, histological examination and the presence of dyslipidemia. The intake of tomato juice led to an accumulation of all - E and Z -lycopene and its metabolites in the livers of these animals; levels were higher in HL than in NL, apparently due to higher absorption (63.07 vs. 44.45 %). A significant improvement in the plasma level of high-density lipoprotein was observed in the HL group compared with HA animals, as was an alleviation of oxidative stress through reduction of isoprostanes in the urine. In relation to fatty acid gene expression, an overexpression of several genes related to fatty acid transport, lipid hydrolysis and mitochondrial and peroxisomal β-fatty acid oxidation was observed in the HL group. Conclusions The consumption of tomato juice and tomato products reduced hallmarks of steatosis, plasmatic triglycerides and very low-density lipoproteins, and increased lipid metabolism by inducing an overexpression of genes involved in more efficient fatty acid oxidation.

Description: Aim Increasing calcium intake is the most effective strategy for avoiding Ca deficit. However, if intake remains inadequate, improving Ca absorption becomes an important tool to optimize Ca homeostasis and bone health. Purpose The effect of a mixture of GOS/FOS ® 9:1 added to a normal- or low-Ca diets on Ca absorption and bone mineralization, density and structure was investigated, in a model of growing rats. Several colonic parameters to help support the findings were also evaluated. Results Weanling Wistar rats received one of the four experimental AIN-93G diets: C5: 0.5 % Ca; C3: 0.3 % Ca; P5: 0.5 % Ca + 5.3 % GOS/FOS ® ; P3: 0.3 % Ca + 5.3 % GOS/FOS ® until 50 days ( T  = 50). At T  = 50, lactobacillus and cecum weights were higher, whereas cecum pH was lower in P5 and P3 versus C5 and C3 ( p  〈 0.001). At T  = 50, fecal Ca, Mg and P were lower and their absorptions (mg/dL) were higher in P5 and P3 versus C5 and C3, respectively ( p  〈 0.05). Ca, Mg and P absorption % was higher in P5 and P3 versus C5 and C3 ( p  〈 0.001). Femur Ca and P content, bone mineral content, trabecular bone mineral density, tibia length, bone volume, osteoblast surface, stiffness and elastic modulus were higher in P5 and P3 versus C5 and C3 ( p  〈 0.05). Despite the lower Ca content, P3 group reached similar values than C5 in all these latter parameters. Conclusions Supplementing diets with the GOS/FOS ® mixture increased bone mineralization, density and structure due to an increase in Ca, P and Mg absorptions. Thus, this prebiotic mixture may help to improve bone development in a period of high calcium requirements.

Description: Background Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status. Methods We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1.1 mg vitamin B 2 , 0.73 mg B 6 , 1.2 μg B 12 and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B 12 status, acetyl- para -aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine. Results Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50 % ( P for difference, P  〈 0.0001). Homocysteine decreased by 1.1 μmol/L compared to baseline, no change was seen in the control group ( P for difference P  〈 0.0001) and acetyl- para -aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention ( P  〈 0.0001). We found no relevant differences between the groups for the cognitive measures. Conclusion Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.

Description: Purpose Pulverized konjac glucomannan (PKGM) is a natural biologically active compound extracted from konjac, a Japanese traditional food. In the present study, we investigated the role of PKGM in intestinal immunity in a mouse model of oxazolone (OXA)-induced colitis. Methods C57BL/6(B6) mice were fed PKGM or control food from 2 weeks before the induction of OXA colitis. Body weight change, colon length, and histological change in the colon were examined. The mononuclear cells were purified from colon and stimulated with PMA/ionomycin. The levels of TNF-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 from the supernatant were measured by ELISA. Results Oral administration of PKGM prevented the body weight loss and shortening of colon length associated with OXA-induced colitis. Histological analysis revealed that the colonic inflammation was improved by the administration of PKGM. The levels of IL-4 and IL-13, the critical inflammatory cytokines in OXA colitis, derived from mononuclear cells from the lamina propria of the colon were significantly suppressed by PKGM administration. PKGM-fed mice showed a significantly lower IL-4/IFN-γ ratio in the colonic lamina propria compared with that in control-fed mice. Fluorescence-activated cell sorting analysis revealed that natural killer (NK) 1.1 + T cells in the liver were significantly decreased in PKGM-fed mice. Finally, the preventive role of PKGM in OXA-induced colitis was not observed in invariant natural killer T cell-deficient mice. Conclusions PKGM ameliorated OXA-induced colitis in mice. This effect is associated with a decreased population of NK1.1 + T cells and induction of Th1-polarized immune responses.

Description: Purpose Resveratrol inhibits lipid accumulation but suffers from limited bioavailability. The anti-depressive agent phenelzine limits adipogenesis in various models of cultured preadipocytes, and this hydrazine derivative also inhibits de novo lipogenesis in mature adipocytes. It was therefore tested whether resveratrol effects on adiposity reduction and glucose tolerance improvement could be reinforced by co-administration with phenelzine. Methods Mice fed a very-high-fat diet (VHFD, 60 % calories as fat) were subjected to drinking solution containing low dose of resveratrol (0.003 %) and/or 0.02 % phenelzine for 12 weeks. Body fat content, glucose tolerance, food and water consumption were checked during treatment while fat depot mass was determined at the end of supplementation. Direct influence of the agents on lipogenesis and glucose uptake was tested in adipocytes. Results Epididymal fat depots were reduced in mice drinking phenelzine alone or with resveratrol. No limitation of body weight gain or body fat content was observed in the groups drinking resveratrol or phenelzine, separately or in combination. The altered glucose tolerance and the increased fat body composition of VHFD-fed mice were not reversed by resveratrol and/or phenelzine. Such lack of potentiation between resveratrol and phenelzine prompted us to verify in vitro their direct effects on mouse adipocytes. Both molecules inhibited de novo lipogenesis, but did not potentiate each other at 10 or 100 μM. Only resveratrol inhibited hexose uptake in a manner that was not improved by phenelzine. Conclusions Phenelzine has no interest to be combined with low doses of resveratrol for treating/preventing obesity, when considering the VHFD mouse model.

Description: Purpose and background The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS). Methods To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis. Results We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM. Conclusions The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.

Description: Purpose The effect of endogenous antioxidants can be either an immediate response (relying on enzymatic activities) or a long-term adaptation (relying on gene modulation events), both susceptible to be modified by antioxidants from diet and supplementation. The aim of this work was to delve in these aspects in circulating white blood cells in a group of volunteers ( n  = 33, 20–22 years) performing eccentric exercises and consuming or not ( n  = 8) different polyphenolic antioxidants ( Lippia citriodora extract-PLX ® n  = 8, almond beverage n  = 9 or a mixture of both n  = 8) during 21 days. Methods We have designed a single-blind, parallel-group, randomized controlled trial. Antioxidant enzyme activities, oxidative stress markers, and antioxidant gene expression were determined. Results Neutrophils and lymphocytes expressed high amounts of oxidative markers compared to plasma. Concerning enzymatic activities, increased superoxide dismutase levels were detected when certain supplements were consumed. However, catalase levels did not change. As for glutathione peroxidase levels, no differences were detected in lymphocytes, while neutrophils expressed increased levels in both placebo and PLX ® groups. Glutathione reductase activity was decreased in all groups, except in neutrophils of PLX ® group. At the level of gene expression, neither PLX ® nor the almond beverage interfered with the expression of genes coding for the corresponding enzymes. However, the combined intake of both supplements affected the expression of glutathione reductase and Cu–Zn and Mn-superoxide dismutases in neutrophils. Conclusions Altogether, these results suggest that blood cell types respond and adapt differently to exercise-induced oxidative damage.

Description: Purpose Fish and rapeseed oil are major sources of omega-3 polyunsaturated fatty acids (n-3 PUFA) in complementary food, but little is known about current consumption in Germany. Methods We conducted a nationwide consumer survey to assess the consumption habits of fish and rapeseed oil and their determining factors in 985 mother–child dyads in Germany. Results One-fourth of infants ate fish as often as recommended, i.e. at least once per week. Half of the mothers stated that they mainly used rapeseed oil for self-prepared and/or commercial vegetable–potato–meat meals. In contrast, mothers more frequently met recommendations for fish consumption (41 %), but used rapeseed oil (34 %) less often for their own nutrition. Maternal eating behaviour was the most important predictor for both of these n-3 PUFA rich foods in infants’ nutrition. In contrast to infants’ fish consumption, rapeseed oil intake in infancy was found to be influenced by some further factors, i.e. mothers’ social class and omega-3 knowledge, which were also key determinants of mothers’ own fish and rapeseed oil consumption. Conclusion To promote fish with complementary feeding, programs should focus on families whose mothers rarely eat fish. Nutritional campaigns to improve omega-3 knowledge—especially focusing on lower social classes—could be effective in increasing rapeseed oil consumption, although these programs should be combined with environmental improvements as it has been already started through the use of rapeseed oil in commercial baby jars.

Description: Purpose Gluten-free products present major challenges for the food industry in terms of organoleptic, technological and nutritional characteristics. The absence of gluten has been shown to affect starch digestibility, thus increasing the postprandial glycaemic response. However, in recent years, gluten-free technologies have been improved, thus possibly modifying this quality parameter. We investigated the glycaemic index (GI) of 10 commercial foods aiming to update the GI values of the most common gluten-free products consumed in Italy. Methods The in vivo GI was evaluated for six bakery products and four types of pasta. The postprandial glucose response was obtained in two groups with 10 healthy volunteers each. Results The overall GI values ranged from 37.5 for breakfast biscuits to 66.7 for puffed multigrain cake. Breads and pasta had GI values consistently lower than those previously reported in the literature. Conclusion The present study showed that several commercial GF products exhibited low and medium GI values, not confirming the previous observations on the high GI of GF. However, considering the multiple formulations and processes for preparation of these products, further studies are recommended.

Description: Purpose Studies in rats suggest that fish proteins may improve lipid and glucose regulation and could thus be a potential tool in the treatment of obesity-related comorbidities. To date, all published rat studies on dietary fish protein have been designed with 50 or 100 % of dietary proteins from fish. As it is not common, nor advised, to consume fish as the only protein source in a healthy diet, mechanistic studies on the effects of diets with low dose fish proteins are needed. Here, we investigate whether a low dose of cod protein would affect glucose homeostasis and lipid metabolism in obese Zucker fa/fa rats. Methods Twelve male obese Zucker fa/fa rats consumed diets where cod proteins accounted for 25 % of the total protein intake with the remaining 75 % from casein (COD) or 100 % of protein as casein (CAS) for 4 weeks. Results Rats fed COD achieved a higher body weight without affecting adiposity and thigh muscle mass after 4 weeks, but liver weight and hepatic cholesterol level were higher than in CAS-fed rats. Fasting serum level of non-esterified fatty acids and 2 h postprandial glucose level were lower in COD than in CAS. The fatty acid metabolism was beneficially affected by the COD diet, with e.g., higher ratio of n-3/n-6 PUFAs in serum, liver and adipose tissue when compared to CAS. Conclusions A low intake of cod protein (25 % of protein intake) was sufficient to beneficially affect lipid metabolism and postprandial glucose regulation in obese fa/fa rats.

Description: Purpose Iodine, bivalent iron (Fe 2+ ), and hydrogen peroxide (H 2 O 2 ), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10 −3  M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff–Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO 3 ), in concentrations corresponding to those typical for Wolff–Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe 2+ +H 2 O 2  → Fe 3+ + · OH + OH − ) substrates. Methods Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO 3 (2.5–50 mM), without/with FeSO 4 (30 µM) + H 2 O 2 (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2′-deoxyguanosine, was measured by HPLC. Results Neither KI nor KIO 3 increased the basal level of 8-oxodG in both nDNA and mtDNA. KI—in all used concentrations—completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO 3 partially prevented Fe 2+ +H 2 O 2 -induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). Conclusions Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO 3 , seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO 3 relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.

Description: Purpose The aim of the present study was to investigate the effects of the consumption of two cloudy apple juices with different polyphenol and vitamin C contents on antioxidant status, cardiometabolic and inflammation markers in healthy young adults. Methods Twenty subjects, aged 21–29 years, completed a randomized crossover study. At each 4-week intervention period, the volunteers randomly consumed two glasses (2 × 250 mL/day) of either a vitamin C-rich apple juice (VCR) (60 mg/L vitamin C and 510 mg catechin equivalent/L) or a polyphenol-rich (PR) juice (22 mg/L vitamin C and 993 mg catechin equivalent/L). Blood and urine samples were collected throughout the study, and markers of antioxidant status, glucose metabolism, lipid profile and inflammation were measured. Results The comparison of the post-intervention minus pre-intervention change revealed differential results in HOMA index, total cholesterol, ICAM-1 and VCAM-1 ( P  〈 0.05) across juices. During the VCR period, plasma antioxidant activity (FRAP) increased ( P  = 0.031), while ICAM-1 and total cholesterol showed a trend to decrease ( P  = 0.060 and P  = 0.094, respectively). During the PR period, plasma insulin and HOMA increased, and total glutathione decreased ( P  〈 0.05). Conclusions A joint consumption of apple juice natural antioxidants such as vitamin C and polyphenols might provide mild favorable effects on cardiometabolic markers, as compared to apple polyphenols alone.

Description: Purpose Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its’ dose–response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Methods Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. Results GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo ( P  〈 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase ( P  〈 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose–response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention ( P  〉 0.05). Conclusion Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. Clinical trial registration: ClinicalTrials.gov, identification number NCT01133899.

Description: Purpose To investigate the presence of anti-angiotensin converting enzyme (ACE) factors in aqueous extract of tomato. Methods The bio-guided fractionation of the aqueous extract of tomato produced a sugar-free, heat-stable fraction with molecular mass 〈1,000 Da from tomatoes. The sugar-free tomato extract (TE) was tested for its anti-ACE activity using human plasma and rabbit lung pure ACE. In addition, its effect on human platelet aggregation induced by ADP, collagen or arachidonic acid was determined. The mechanism of platelet inhibitory action of TE was investigated by measuring platelet factor 4 (PF4) release and cAMP synthesis by platelets. Results Typically, 100 g tomatoes produced 72.2 ± 4.7 mg of TE. This extract inhibited both platelet aggregation and plasma ACE activity in a dose-dependent manner. It inhibited platelet aggregation in response to ADP, collagen or arachidonic acid, and inhibitory action was mediated in part by reducing platelet PF4 release and by stimulating cAMP synthesis. The IC 50 value of TE for ADP-induced platelet aggregation was 0.4 ± 0.02 mg/ml, whereas the IC 50 value for ACE enzyme inhibition was 1.40 ± 0.04 mg/ml. Both the TE and commercially available sugar-free TE, Fruitflow ® -2 had similar amount of catechin, and also had equal inhibitory potencies against platelet aggregation and plasma ACE activity. Conclusion Together these data indicate that aqueous extract of tomatoes contain anti-ACE factors in addition to previously described anti-platelet factors.

Description: Purpose Maternal obesity is a risk factor for metabolic diseases in offspring. The aim of this study was to investigate whether quercetin administration during gestation and lactation could have any protective effect against the impact of maternal obesity on increased sensitivity to obesity and metabolic disorders in offspring. Methods Female Sprague–Dawley rats were fed a high-fat diet to induce obesity. Obese dams were administered 0, 50, 100 or 200 mg/kg body weight (BW) quercetin intragastrically during gestation and lactation. Normal weight dams were used as controls. The F1 generation was fed with a standard diet after weaning, and blood glucose, lipids and inflammatory factors were assessed. Expression of biomarkers involved endoplasmic reticulum (ER) stress, and related inflammatory pathways in liver and adipose tissues were analyzed at postnatal day 100. Results Maternal obesity resulted in increased birth weight, postnatal BW gain, hyperglycemia, hyperlipemia, hyperinsulinemia, increased serum levels of inflammatory factors, and up-regulated biomarkers involved in ER stress and related inflammatory pathways in the offspring. Maternal quercetin intervention (QI) had significant ameliorating effects on maternal blood lipids, especially cholesterol, which resulted in improved glucose metabolism and insulin sensitivity and alleviated ER stress and related inflammation in the grown offspring of obese dams. Conclusions Maternal QI in obese dams during gestation and lactation reduced birth weight and postnatal BW gain in the offspring, and helped to improve insulin sensitivity and lipid metabolism of the mature offspring via reducing ER stress and related inflammation in the liver and adipose tissue.

Description: Purpose Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans . Methods Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects. Results Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev - 1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf -2, daf - 16 , pmk - 1 , and skn - 1 . Conclusions Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn - 1 (encoding a component of the p38 MAPK pathway) and daf - 16 (encoding a component of the IGF-1 pathway).

Description: Purpose Recently, we reported that preferential maternal–fetal vitamin C (vitC) transport across the placenta is likely to be impaired by prolonged maternal vitC deficiency. Maintenance of a basal maternal vitC supply at the expense of the fetus may impair fetal development; however, the knowledge of vitC’s impact on intrauterine development is sparse. The aim of this study was to explore the effect of maternal vitC status on fetal and placental development in guinea pigs. Methods Twenty pregnant Dunkin Hartley guinea pigs were randomized into four groups to receive diets either sufficient (918 mg/kg CTRL) or deficient (100 mg/kg DEF) in vitC. Cesarean sections at gestational day (GD) 45 or 56 allowed for fetal and placental measurements. Results At GD45, body, brain and placental weights were significantly reduced in DEF pups compared with CTRL ( p  〈 0.05, p  〈 0.001 and p  〈 0.05, respectively). DEF plasma vitC levels were ~6 % of those of CTRL ( p  〈 0.0001), and the fetal/maternal plasma vitC ratio was significantly reduced at GD56 in the DEF animals compared with controls ( p  = 0.035). Placental vitC levels were reduced in DEF animals ( p  〈 0.0001) and the ascorbate oxidation ratio and glutathione elevated compared with controls ( p  〈 0.0001). Conclusions Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Low maternal vitC intake during pregnancy may compromise maternal weight gain, placental function and intrauterine development.

Description: Purpose The aim of the present study was to examine the effects of consumption of desserts with low glycemic index (GI) and low glycemic load (GL), as part of a balanced hypo-caloric diet, on anthropometric and biochemical parameters in patients with type 2 diabetes mellitus (T2DM). Methods A total of 61 subjects with T2DM were randomly assigned to the intervention ( n  = 30) or to the control group ( n  = 31). Both groups followed the same hypo-caloric (−500 kcal) diet for 12 weeks. Consumption of four portions of low-GI/low-GL desserts/week was included in the diet in the intervention group while one portion of a favorite usual sweet/week was allowed to be consumed in the control group. Results Thirty subjects in the control and 28 subjects in the intervention group completed the trial. Body weight, body mass index, and waist circumference were reduced significantly in both groups. Arterial blood pressure, fasting blood glucose, glycosylated hemoglobin, insulin, and γ-GT were reduced significantly only in the intervention group; however, there were no significant differences between the two groups at endpoint. C-reactive protein was reduced in the intervention, and HDL cholesterol was also reduced in the control group; the reductions were significantly different at the end of the trial. No significant changes were observed in the other plasma lipids, uric acid, leptin, adiponectin, and interleukin-6 in either study group. Conclusions Consumption of desserts with low GI/GL in a balanced hypo-caloric diet has a positive impact on anthropometric and metabolic parameters of patients with T2DM.

Description: Purpose The aim of this study was to study the association between the consumption of energy-dense foods at 2 years and body mass index (BMI) at 4 years, using a cross-lagged panel design. Methods The present study included 589 children evaluated at 2 and 4 years of age, as part of the birth cohort generation XXI. Information was obtained by face-to-face interviews. Consumption of energy-dense foods (salty snacks, soft drinks, cakes, and sweets) was measured using a food frequency questionnaire. Children’s weight and height were measured by standard procedures, and BMI standard deviation scores (BMI z -scores) were calculated according to the World Health Organization. Linear regression and cross-lagged panel design models were fitted to estimate the associations between the consumption of energy-dense foods and BMI z -scores (controlled for maternal age, education and prepregnancy BMI, and children’s exact age at 2 years). Results The consumption of energy-dense foods at 2 years was significantly associated with their consumption at 4 years ( β  = 0.522, 95 % CI 0.432–0.612). Children’s BMI z -scores at 2 years were associated with posterior BMI z -scores ( β  = 0.747, 95 % CI 0.688–0.806). In the cross-lagged analysis, consumption of energy-dense foods at 2 years had no effect on subsequent BMI z -scores ( β  = −0.030, 95 % CI −0.095 to 0.035) and BMI z -scores at 2 years were not significantly associated with the consumption of energy-dense foods at 4 years ( β  = −0.012, 95 % CI −0.086 to 0.062). Conclusions Consumption of energy-dense foods and BMI tracked over time, but the consumption of energy-dense foods at 2 years was not associated with BMI z -scores at 4 years.

Description: Background Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities. Purpose We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1β-stimulated Caco-2 cells. Methods HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1β. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. Results HPE decreased prostaglandin (PG)E 2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. Conclusion Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.

Description: Purpose The hypothesis was tested that coffee types differing in content of major constituents also differ with regard to cardiometabolic effects. Methods Overweight persons ( n  = 118) were randomized to consume a dark roast [rich in N -methylpyridinium (NMP)] or medium roast (rich in caffeoylquinic acids, trigonelline) coffee blend for 3 months, after a washout period of 4 weeks. Before and after the intervention period, body weight and 15 further general and biochemical parameters were determined. Results Participants consumed an average of 4–5 cups per day. Mean body weight, body mass index and waist circumference did not change during the coffee consumption phase in either of the study groups. Systolic blood pressure decreased in the dark roast coffee group only ( p  〈 0.05). High-density lipoprotein cholesterol levels increased in the medium roast coffee group only, and triglyceride levels increased in the dark roast coffee group only. Glucoregulation and insulin levels were not affected, although there was a small increase of hemoglobin A1c values in both groups. An increase of adiponectin levels occurred in the medium roast coffee group only and was negatively associated with NMP concentrations. Differences did not remain statistically significant after correction for multiple testing. Conclusions Medium and dark roast coffee blends exert small but possibly relevant different cardiometabolic effects. Further studies of health outcomes in relation to coffee constituents seem warranted.

Description: Purpose Greater body fatness has been associated with increased risk of gout in several studies; however, the strength of the association has differed between studies, and it is not clear whether the association differs by gender. We conducted a systematic review and meta-analysis of prospective studies to clarify the association between adiposity and risk of gout. Methods PubMed and Embase were searched up to August 30, 2013. Summary relative risks (RRs) were calculated using a random effects model. Results Ten prospective studies of body mass index (BMI) and gout risk with 27,944 cases and 215,739 participants were included (median follow-up 10.5 years). The summary RR for a 5 unit increment was 1.55 [95 % confidence interval (95 % CI) 1.44–1.66, I 2  = 67 %] for all studies combined. The heterogeneity was explained by one study, which appeared to be an outlier. The summary RR per 5 BMI units was 1.62 (95 % CI 1.33–1.98, I 2  = 79 %) for men and 1.49 (95 % CI 1.32–1.68, I 2  = 30 %) for women, p heterogeneity  = 0.72. The relative risks were 1.78, 2.67, 3.62, and 4.64 for persons with BMI 25, 30, 35, and 40 compared with persons with a BMI of 20. BMI in young adulthood, waist-to-hip ratio, and weight gain from age 21–25 to midlife were also associated with increased risk, but few studies were included in these analyses. Conclusions Greater body mass index increases risk of gout. Further studies are needed on adiposity throughout the life course, waist-to-hip ratio, and weight changes in relation to gout as there were few studies that had published on these exposures.

Description: Purpose Regular nut consumption is inversely associated with cardiovascular disease risk. No study has compared the effects of regular consumption of different types and forms of nuts on acceptance, which is a crucial determinant of long-term compliance to consume nuts regularly. Methods This study examined the effects of different types and forms of raw, unpeeled nuts on acceptance and the effects of nut consumption on blood lipids through a randomised crossover study with six dietary phases: 30 g/day of ground, sliced, or whole almonds or hazelnuts for 5 days each ( n  = 74). Acceptance (‘desire’ and ‘liking’) for nuts was measured daily using visual analogue scales. Blood lipids were measured at baseline and week 6. Results Acceptance was stable over all conditions, but there were differences between nut forms (ground 〈 sliced 〈 whole, P  〈 0.001 for both ‘desire’ and ‘liking’) with some nut type–nut form interactions. Compared with baseline, week 6 HDL-C was higher (0.06 mmol/L, 95 % CI 0.02–0.10, P  = 0.002) while LDL-C and total-C:HDL-C ratio were lower (0.15 mmol/L, 95 % CI 0.06–0.25, P  = 0.002 and 0.25, 95 % CI 0.07–0.43, P  = 0.006). Conclusions In conclusion, acceptance was stable for all combinations but was highest for whole nuts. Six weeks of nut consumption improved blood lipids.

Description: Purpose This study explored the in vitro antioxidant and anti-platelet activities of hydroxytyrosol, hydroxytyrosol acetate, 3,4-dihydroxyphenylglycol and two phenolic olive extracts. These compounds and extracts were obtained from a new industrial process to hydrothermally treat the alperujo (160 °C/60 min), a by-product of olive oil extraction. Methods The extracts and the purified compounds were obtained chromatographically using both ionic and adsorbent resins. The antioxidant activity was determined by measuring inhibition of human platelet aggregation and inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats. Results The positive effect of the extracts on the inhibition of platelet aggregation is showed, being higher in the case of hydroxytyrosol acetate up to 38 %, and for the first time, its synergist effect with hydroxytyrosol has been proved, obtaining more than double of inhibition. The phenolic extracts and the isolated phenols showed good results for inhibiting the lipid oxidation, up to 62 and 25 %, respectively. A synergistic effect occurred when the hydroxytyrosol acetate and the 3,4-dihydroxyphenylglycol were supplemented by hydroxytyrosol. Conclusion These results suggest the extract and these compounds obtained from a novel industrial process could be natural alternatives for the prevention of diseases related to cardiovascular disorder or oxidative damage.

Description: Purpose In Caucasian women, research has shown that energy balance and taste preference change throughout the menstrual cycle. However, the contributory role of the menstrual cycle to obesity and insulin resistance among Asian women remains unclear. We investigate the impact of the menstrual cycle on energy balance and taste preference in Singaporean Chinese females. Methods Thirty-one healthy young Chinese female subjects with regular menstrual cycles were recruited. Anthropometrics, body composition, energy intake, resting metabolic rate, premenstrual syndrome (PMS) severity and taste preference to sucrose were assessed during three phases (menses, follicular and luteal), over one ( N  = 18) to two ( N  = 13) menstrual cycles. Results For all subjects ( N  = 31), we found significant reductions in energy, fat intake ( p  〈 0.05) and taste preference for sucrose ( p  〈 0.05) in the luteal phase compared to early follicular phase as far as Cycle 1 is concerned. No significant differences were observed for carbohydrate and protein intake as well as PMS score. In those evaluated for two full cycles ( N  = 13), we found that taste preference for sucrose and PMS score were significantly higher in the menstrual phase in Cycle 2 ( p  〈 0.05). No significant differences were observed in energy and macronutrient intake throughout Cycle 2. RMR was similar across the three phases. However, non-significant cyclic variations were noted within and between the cycles. Conclusion Cyclic variations in energy intake and expenditure contributed by sensory and behavioural changes occur during the menstrual cycle. Whether this contributes to cyclic weight gain is speculative and remains to be proven. Further research in non-Caucasians spanning more than one menstrual cycle is needed to establish the impact of the menstrual cycle on taste preference and energy balance.

Description: Purpose During the postnatal stage, cardiovascular nitric oxide (NO) system and caveolins (cav) may be regulated differentially in response to hypovolemic state induced by water restriction. Our aim was to examine the effects of water restriction on NO synthases (NOS) and cav in the atria, ventricle and aorta of growing rats. Methods Male Sprague–Dawley rats aged 25 and 50 days were divided into ( n  = 15): WR: water restriction 3 days; WAL: water ad libitum 3 days. Systolic blood pressure, NOS activity and NOS/cav protein levels were measured. Results Dehydration induced a larger increase in SBP in WR25 group. Ventricular NOS activity, endothelial NOS (eNOS) and neuronal isoform (nNOS) of WR25 pups were increased, and both cav were decreased. In the WR50 group, NOS activity remained unchanged. In the atria, NOS activity, eNOS and nNOS decreased in WR25 associated with increased cav-1; in the WR50 group, NOS activity was increased without changes in NOS isoforms. In the aorta of WR25, NOS activity and inducible NOS (iNOS) were decreased; NOS activity was unchanged in WR50, despite the decreased levels of eNOS and increased iNOS, cav-1 and cav-3. Conclusions NO system adjustments in cardiovascular system under osmotic stress in vivo depend on postnatal age, being eNOS and nNOS, the isoforms that determine NOS activity in cardiac tissue in 25-day-old pups. Changes in cav abundance during hypovolemic state may contribute to age-related NO production.

Description: Purpose In terms of their involvement in allergic and inflammatory conditions, mast cells (MC) can be promising targets for medical agents in therapy. Because of their good compliance and effectiveness, phytochemicals are of great interest as new therapeutic tools in form of nutraceuticals. We found recently that cinnamon extract (CE) inhibits mast cell activation. Here, we analysed the effects of a major compound of CE, cinnamaldehyde (CA), on mast cell activation. Methods Release of prestored and de novo synthesised mediators as well as expression of pro-inflammatory cytokines and mast cell-specific proteases were analysed in RBL-2H3 cells or in human mast cells isolated from intestinal tissue (hiMC) treated with CA prior to stimulation by FcεRI crosslinking or IONO/PMA. The results were compared with the corresponding effects of CE. Results Following treatment with CA, release of β-hexosaminidase in IgE-dependent or IgE-independent activated RBL-2H3 cells was down-regulated in a dose-dependent manner to about 10 %. In hiMC, release of β-hexosaminidase was also significantly reduced, and release of LTC 4 and CXCL8 was almost completely inhibited by CA. Moreover, IgE-mediated expression of CXCL8 , CCL2 , CCL3 and CCL4 in hiMC was significantly down-regulated by CA. With the exception of the expression of the mast cell proteases tryptase and chymase , the inhibitory effects of CA were very similar to the effects shown for CE treatment. The reducing effect of CA on mast cell mediators—seen for long- and for short-term incubations—could be related to particular signalling pathways as CA caused a down-regulation in ERK as well as PLCγ1 phosphorylation. Conclusions CA decreases release and expression of pro-inflammatory mast cell mediators. This inhibitory action is similar to the effects observed for CE indicating CA as the main active compound in CE leading to its anti-allergic properties.

Description: Purpose Although previous research has associated the glycaemic load (GL) of a meal with cognitive functioning, typically the macro-nutrient composition of the meals has differed, raising a question as to whether the response was to GL or to the energy, nutrients or particular foods consumed. Therefore, the present study contrasted two breakfasts that offered identical levels of energy and macro-nutrients, although they differed in GL. Methods Using a repeated-measures, double-blind design, 75 children aged 5–11 years, from socially deprived backgrounds, attended a school breakfast club and on two occasions, at least a week apart, they consumed a meal sweetened with either isomaltulose (Palatinose™) (GL 31.6) or glucose (GL 59.8). Immediate and delayed verbal memory, spatial memory, sustained attention, reaction times, speed of information processing and mood were assessed 1 and 3 h after eating. Results The nature of the meals did not influence any measure of cognition or mood after an hour; however, after 3 h, children’s memory and mood improved after the lower-GL breakfast. If children had eaten the lower-GL meal on the second day of testing, they were able to process information faster and had better spatial memory later in the morning. Conclusions Towards the end of a morning in school, having consumed a lower-GL breakfast resulted in better mood and aspects of cognitive functioning.

Description: Purpose Recently, controversies have arisen concerning the association between nut intake and obesity. This study was performed to investigate the relationship between nut consumption and obesity among Iranian adults. Methods In a cross-sectional survey, 9,660 randomly chosen adults aged ≥19 years were selected based on gender, age and their settlement distributions in three districts of central Iran in 2007. Nutritional behaviors including regular intake of walnuts, almonds, pistachios, hazelnuts and sunflower seed were assessed by validated 48-item-food-frequency questionnaire and a 24-h recall questionnaire. Using hierarchical logistic regression test, odds ratio (OR) 95 % CI of obesity based on nut consumption was determined in an unadjusted and four adjusted models. Results The results showed a significant association between high nut consumption and lower prevalence of overweight or general obesity as well as abdominal obesity in women ( p  = 0.01 and p  = 0.047, respectively), but not men. The frequency of nut consumption was associated with lower risk of overweight or general obesity [OR (95 % CI) 0.57 (0.38–0.86)] and abdominal obesity [OR (95 % CI) 0.51 (0.28−0.95)] only in women. After adjusting for gender, age and other potential confounders, the strength of the associations was blunted, but they were still significant. Conclusions Frequent nuts and seeds consumption, particularly ≥1 time/day, had an inverse association with all classes of obesity among women.

Description: Purpose It was hypothesised that blackcurrant seed oil beneficially modulates metabolic disorders related to obesity and its complications. The study also aimed to investigate the potentially adverse effects of an unbalanced diet on the distal intestine. Methods Male Wistar rats were randomly assigned to four groups of eight animals each and were fed a basal or obesogenic (high in fat and low in fibre) diet that contained either rapeseed oil (Canola) or blackcurrant seed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. Results After 8 weeks, the obesogenic dietary regimen increased the body weight, altered the plasma lipid profile and increased the liver fat content and the plasma transaminase activities. In addition, the obesogenic diet decreased bacterial glycolytic activity and short-chain fatty acid formation in the distal intestine. Dietary blackcurrant seed oil improved the lipid metabolism by lowering liver fat accumulation and the plasma triglyceride concentration and atherogenicity as well by increasing the plasma HDL-cholesterol concentration. However, in rats fed an obesogenic diet containing blackcurrant seed oil, the plasma HDL-cholesterol concentration was comparable with both rapeseed oil-containing diets, and a significant elevation of the plasma transaminase activities was noted instead. Conclusions The obesogenic dietary regimen causes a number of metabolic disorders, including alterations in the hindgut microbial metabolism. Dietary blackcurrant seed oil ameliorates the lipid metabolism; however, the beneficial effect is restricted when it is provided together with the obesogenic diet, and a risk of liver injury may occur.

Description: Purpose To investigate the mechanisms of impairments in oxidative metabolism in obese and diabetic (T2DM) skeletal muscle, this study analysed the adaptive expression of genes involved in fatty acid (FA) oxidation and mitochondrial biogenesis in primary myotubes treated with elevated FAs. Methods Muscle samples from obese or obese T2DM donors were stored or processed into human primary skeletal muscle myotubes, which were treated for 6 h with a saturated (palmitic acid) or a monounsaturated (oleic acid) FA with or without a polyunsaturated FA (eicosapentaenoic acid: EPA). Real-time PCR analysis was used to determine mRNA expression. Results Basal pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in whole muscle samples from obese and T2DM subjects was increased compared to lean ( P  〈 0.05; n  = 13–20/group). In obese- and T2DM-derived myotubes, oleic acid treatment alone and in combination with EPA increased PDK4 mRNA expression compared to control ( P  〈 0.05; n  = 7/group), whereas palmitic acid alone and in combination with EPA only increased PDK4 mRNA in T2DM-derived myotubes compared to control ( P  〈 0.05; n  = 7/group). EPA alone did not alter mRNA expression of PDK4. Conclusions These findings show that FAs induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors. This persistent difference in PDK4 expression, present after culturing, suggests a fundamental alteration in the FA-mediated gene expression. This may in turn translate to differences in the regulation of oxidative substrate flux to impact on insulin sensitivity.

Description: Purpose This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits. Methods The experiments were carried out with 24 male rabbits randomly divided into four groups: KO—castrated, treated with KO; FO—castrated, treated with FO; C—castrated, non-treated; NC—non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits. Results Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 ( Cpt2 ) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 ( Hmgcs2 ) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha ( Acaca ) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group. Conclusion The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in β-oxidation and lipogenesis in liver and skeletal muscle.

Description: Purpose We tested the hypothesis that maternal low-protein (LP) diet during gestation and lactation can program myostatin (MSTN) signaling and protein synthesis in skeletal muscle of offspring at weaning stage (35 days). Methods Fourteen Meishan sows were fed either LP or standard-protein diets throughout gestation and lactation, male offspring piglets were killed at weaning stage and longissimus dorsi (LD) muscles were taken. The cross-sectional areas (CSA) of LD muscles were measured by hematoxylin and eosin staining. The levels of free amino acids in plasma were measured by amino acid auto-analyzer. Proteins and mRNA were determined by Western blot and RT-qPCR, respectively. Results Body weight, LD muscle weight and the myofiber CSA were significantly decreased ( P  〈 0.05) in LP piglets; meanwhile, the concentration of branched-chain amino acids was also significantly decreased ( P  〈 0.001). MSTN protein content tended to be higher ( P  = 0.098) in LP piglets, while the expression of MSTN receptors, activin type II receptor-beta and transforming growth factor type-beta type I receptor kinase, was significantly up-regulated ( P  〈 0.05). Furthermore, p38 mitogen-activated protein kinase, the downstream signaling factor of MSTN, was also enhanced significantly ( P  〈 0.05). In addition, key factors of translation initiation, phosphorylated eukaryotic initiation factor 4E and the 70 kDa ribosomal protein S6 kinase, were significantly decreased ( P  〈 0.05) in LP piglets. Conclusions Our results suggest that maternal LP diet during gestation and lactation affects MSTN signaling and protein synthesis in skeletal muscle of offspring at weaning stage.

Description: Purpose Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Methods Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups ( n  = 7–11 per group). Results PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring ( P  〈 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity ( P  〈 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P  〈 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. Conclusions These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

Description: Purpose The potential association between endometriosis and coffee/caffeine consumption has been analysed in several epidemiological studies. In order to establish whether caffeine influences the risk of endometriosis, we provide to summarize the evidence from published studies on this issue. Methods We performed a meta-analysis of epidemiological studies published up to January 2013. We computed summary relative risks (RR) of endometriosis for any, high and low versus no coffee/caffeine consumption. Results We identified a total eight studies, six case–control and two cohort studies, including a total of 1,407 women with endometriosis. The summary RR for any versus non-consumption were 1.26 [95 % confidence interval (CI) 0.95–1.66] for caffeine and 1.13 (95 % CI 0.46–2.76) for coffee consumption; the overall estimate was 1.18 (95 % CI 0.92–1.49). The summary RR were 1.09 (95 % CI 0.84–1.42) and 1.09 (95 % CI 0.89–1.33) for high and low caffeine consumption as compared to no consumption, respectively. Conclusion The present meta-analysis provided no evidence for an association between coffee/caffeine consumption and the risk of endometriosis. Coffee/caffeine consumption, as currently used in diet, does not carry a health risk.

Description: Purpose Although previous literature has reported that regular green tea consumption may improve blood pressure, the evidence from these studies is not consistent. The present study systematically reviewed randomised controlled trials and examined the effect of green tea consumption on blood pressure using meta-analysis. Methods Search of ProQuest, PubMed, Scopus and Cochrane Library (CENTERAL) was conducted, to identify eligible articles. Articles from 1995 to 2013 were included. A random-effect model was chosen to calculate the effect of combined trials. Result Thirteen studies were included in the meta-analysis. Green tea consumption significantly changed systolic blood pressure, by −2.08 mm Hg (95 % CI −3.06, −1.05), and diastolic blood pressure, by −1.71 mm Hg (95 % CI −2.86, −0.56), compared to the control. Changes in lipid profile, blood glucose and body mass index were also assessed in the meta-analysis. A significant reduction was found in total cholesterol (−0.15 mmol/L [95 % CI −0.27, −0.02]) and low-density lipoprotein cholesterol (−0.16 mmol/L [95 % CI −0.22, −0.09]). Changes in other parameters did not reach statistical significance. Subgroup analysis suggested a greater reduction in both systolic and diastolic blood pressure in studies that included participants with a baseline mean systolic blood pressure of ≥130 mm Hg, and studies involving consuming green tea as an extract. Conclusion The present meta-analysis suggests that green tea and its catechins may improve blood pressure, and the effect may be greater in those with systolic blood pressure ≥130 mm Hg. The meta-analysis also suggests that green tea catechins may improve total and low-density lipoprotein cholesterol.

Description: Purpose At northern latitudes, vitamin D is not synthesized endogenously during winter, causing low plasma 25-hydroxyvitamin D (25(OH)D) concentrations. Therefore, we evaluated the effects of a healthy Nordic diet based on Nordic nutrition recommendations (NNR) on plasma 25(OH)D and explored its dietary predictors. Methods In a Nordic multi-centre trial, subjects ( n  = 213) with metabolic syndrome were randomized to a control or a healthy Nordic diet favouring fish (≥300 g/week, including ≥200 g/week fatty fish), whole-grain products, berries, fruits, vegetables, rapeseed oil and low-fat dairy products. Plasma 25(OH)D and parathyroid hormone were analysed before and after 18- to 24-week intervention. Results At baseline, 45 % had vitamin D inadequacy (〈50 nmol/l), whereas 8 % had deficiency (〈25 nmol/l). Dietary vitamin D intake was increased by the healthy Nordic diet ( P  〈 0.001). The healthy Nordic and the control diet reduced the prevalence of vitamin D inadequacy by 42 % ( P  〈 0.001) and 19 % ( P  = 0.002), respectively, without between-group difference ( P  = 0.142). Compared with control, plasma 25(OH)D ( P  = 0.208) and parathyroid hormone ( P  = 0.207) were not altered by the healthy Nordic diet. Predictors for 25(OH)D were intake of vitamin D, eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA), vitamin D supplement, plasma EPA and plasma DHA. Nevertheless, only vitamin D intake and season predicted the 25(OH)D changes. Conclusion Consuming a healthy Nordic diet based on NNR increased vitamin D intake but not plasma 25(OH)D concentration. The reason why fish consumption did not improve vitamin D status might be that many fish are farmed and might contain little vitamin D or that frying fish may result in vitamin D extraction. Additional ways to improve vitamin D status in Nordic countries may be needed.

Description: Purpose The present study analyzes the effect of the replacement of dietary casein by soy protein on the mechanisms underlying dyslipidemia, liver steatosis and altered glucose and lipid metabolism in the skeletal muscle which developed in rats fed long-term a sucrose-rich diet (SRD). Methods Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD, and the other half were fed a SRD in which the source of protein casein was replaced by soy. The control group received a diet with cornstarch as source of carbohydrate. Results Compared to SRD-fed animals, the rats fed soy showed: A—in the liver: reduction of triglyceride and cholesterol storage and decreased steatosis; normalization of mature forms of the protein mass levels of SREBP-1 and the activities of lipogenic enzymes, while the protein mass level of PPAR-α and fatty acid oxidase activity increased. B—in the gastrocnemius muscle: normalization of the enhanced lipid storage and the altered glucose oxidation, improving glucose phosphorylation; decreasing protein mass level of nPKCθ in the membrane fraction; reversion of the impaired insulin-stimulated glucose transporter Glut-4, and glucose-6-phosphate and glycogen concentrations. Besides, dyslipidemia and glucose homeostasis returned to control values. Conclusions This study provides new information concerning some key mechanisms related to the effect of dietary soy on hepatic lipid metabolism and insulin action in the skeletal muscle in the presence of pre-existing dyslipidemia and insulin resistance induced by a SRD.

Description: Introduction There is still a scientific debate on the exact role played by obesity on stroke risk. Objective The aim of the study was to analyze the association between obesity, measured by different indices such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a new one called A Body Shape Index (ABSI) and the risk of total and ischemic stroke. Subjects/methods A total of 41,020 subjects (15,490 men and 25,530 women) aged 29–69 years participated in the study. All participants were recruited between 1992 and 1996 and followed up until 2008 to ascertain incident cerebrovascular disease events. Cox proportional hazards models were designed to estimate the relative risk and 95 % CI between obesity and cerebrovascular disease incidence. Results After 13.8 years of follow-up, a total of 674 stroke cases (55.3 % in men) were registered (531 ischemic, 79 hemorrhagic, 42 subarachnoid hemorrhage and 22 unspecified). WC fourth quartile (HR 1.95; 95 % CI 1.20–3.19) and WHR fourth quartile (HR 1.58; 95 % CI 1.12–2.25) were positively associated with total stroke only in men. BMI was not associated with stroke incidence. The new index, ABSI, was significantly associated with total stroke incidence only in men (HR 1.54; 95 % CI 1.06–2.23). Conclusions Data from the Spanish EPIC cohort study show a strong association of WC and WHR with the relative risk of suffering a stroke only in men, while no associations were found for BMI. It supports the suggestion of other authors of using more than one obesity index in the study of stroke risk prediction.

Description: Purpose Body weight in young growing and young adult animals was reduced by a high dietary density of whey protein concentrate; however, it is unclear whether dietary proteins similarly affect body weight in aging animals. Here, we examined whether whey protein or whey peptide ingestion suppressed body fat accumulation and affected protein expression and phosphorylation in skeletal muscle in aging mice. Methods Twenty-six male senescence-accelerated mouse prone 6 (SAMP6) mice were assigned randomly to three dietary treatment groups: 18.7 % casein control (CON), 18.7 % whey protein (WPR), and 18.7 % whey peptide (WPE). After 28 weeks of treatment, skeletal tissues were dissected and weighed for analysis. Western blotting was performed to examine the expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and adipose triglyceride lipase (ATGL) in quadriceps muscles. Results Body (CON: 47.6 ± 2.2 g, WPR: 48.2 ± 2.7 g, WPE: 38.3 ± 2.0 g) and relative white adipose tissue (CON: 38.5 ± 3.5 mg/g, WPR: 43.8 ± 4.0 mg/g, WPE: 21.1 ± 4.4 mg/g) weights were lower in the WPE group compared with the other two groups ( p  〈 0.05), and no significant differences were observed between the CON and WPR groups. The relative weights of tibialis anterior muscle (CON: 1.04 ± 0.04 mg/g, WPR: 0.97 ± 0.03 mg/g, 1.23 ± 0.05 mg/g) and gastrocnemius muscle (CON: 3.02 ± 0.12 mg/g, WPR: 2.92 ± 0.15 mg/g, WPE: 3.65 ± 0.18 mg/g) were higher in the WPE group compared with the other groups ( p  〈 0.05). The phosphorylation of AMPK (WPR: 1.03 ± 0.11, WPE: 1.36 ± 0.12; fold change from control) and ACC (WPR: 1.08 ± 0.07, WPE: 1.18 ± 0.05; fold change from control) in WPE was higher than in CON ( p  〈 0.05). There were no significant differences in the expression levels of ATGL among the three groups. Conclusions These data suggest that a normal (or moderate excess) dietary density of whey peptide attenuates body fat accumulation via upregulation of fatty acid oxidation in skeletal muscle in aging mice.

Description: Purpose Although a role of glycemic index (GI) and glycemic load (GL) in age-related cataract development is plausible, a few studies, all conducted in USA or Australia, provided results on this issue. The aim of the present study was to provide new original data from a Mediterranean population. Methods We analyzed data from an Italian case–control study including 761 cases with cataract extraction and 1,522 hospital controls, frequency-matched with cases by center, sex, and age. Multivariate odds ratios (ORs) for GI and GL intakes were obtained from logistic regression models after allowance for major confounding factors, including non carbohydrate energy intake, smoking, and diabetes. Results The ORs of cataract extraction for the highest versus the lowest tertile were 1.20 (95 % confidence interval, CI 0.91–1.57) for GI and 1.57 (95 % CI 1.16–2.13) for GL, with a statistically significant trend in risk for GL ( p  〈 0.01). Results were materially unchanged when diabetics were excluded from the analysis. No heterogeneity emerged across strata of sex, age, education, smoking habits and body mass index. Conclusions The present study supports a positive association between dietary GL and the risk of cataract extraction, independently from diabetes, and a lack of association for GI.

Description: Purpose Previous epidemiological studies on egg consumption and the risk of gastrointestinal (GI) neoplasms suggest a positive association; however, data are limited and the evidence remains controversial. This study aims to investigate and quantify the potential dose–response relationship with an evaluation of cancer site-specific differences. Methods Relevant studies were identified after the literature search via electronic databases until January 2014. Subgroup analysis for serving portions was performed using two standardized classification methods: (1) less than 3, or 3 or more eggs per week; (2) less than 3, 3–5, or more than 5 eggs per week. Method two excludes studies that only reported consumption frequency. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random-effects model. Results Thirty-seven case–control and seven cohort studies were included for meta-analysis, which contained a total of 424,867 participants and 18,852 GI neoplasm cases. The combined odds ratio (OR) was calculated to 1.15 (95 % CI 1.09–1.22; p value heterogeneity 〈0.001), showing only a slight increase in risk. The correlation was stronger for colon cancers 1.29 (95 % CI 1.14–1.46; p value heterogeneity 〈0.22). Dose–response analysis revealed similar results with stratification methods, and the ORs for an intake of 〈3 and ≥3 eggs per week were 1.14 (95 % CI 1.07–1.22; p value heterogeneity = 0.38) and 1.25 (95 % CI 1.14–1.38; p value heterogeneity = 0.25), respectively. With method 2, the ORs for an intake of 〈3, 3–5, and 〉5 eggs per week were 1.13 (95 % CI 1.06–1.21; p value heterogeneity = 0.25), 1.14 (95 % CI 1.01–1.29; p value heterogeneity = 0.06), and 1.19 (95 % CI 1.01–1.39; p value heterogeneity 〈0.001), respectively. Conclusion This study provides evidence that egg consumption is associated with a positive dose–response association with the development of GI neoplasms.

Description: Purpose Coffee and green tea consumption may be associated with circulating adipokines, but data are inconsistent, scarce or lacking. We examined the association of coffee and green tea consumption with serum adiponectin, leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1) among a Japanese working population. Methods The authors analyzed data ( n  = 509) from a cross-sectional survey among Japanese workers aged 20–68 years. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Coffee and green tea consumption was assessed using a validated diet history questionnaire, and caffeine consumption from these beverages was estimated. Multiple regression analysis was performed with adjustment for potential confounding variables. Results Coffee consumption was significantly, inversely associated with leptin and PAI-1 ( P for trend = 0.007 and 0.02, respectively); compared with subjects consuming 〈1 cup per day, those consuming ≥4 cups per day had 13 and 10 % lower means of leptin and PAI-1, respectively. Similar associations were observed for caffeine consumption ( P for trend = 0.02 for both leptin and PAI-1). Additionally, we noted a significant positive association between coffee consumption and adiponectin in men ( P for trend = 0.046), but not in women ( P for trend = 0.43, P for interaction = 0.11). Moreover, there was a positive association between coffee consumption and resistin in current male smokers ( P for trend = 0.01), but not in male non-smokers ( P for trend = 0.35, P for interaction = 0.11). Green tea consumption was not associated with any adipokine. Conclusions Higher consumption of coffee and caffeine but not green tea was associated with lower serum levels of leptin and PAI-1 in Japanese adults.

Description: Purpose The deficiency of glutathione (GSH) has been linked to several diseases. The study investigated the role of GSH as a protective factor against hyperglycemia-mediated injury in VL-17A cells treated with 50 mM glucose. Methods The cell viability and different oxidative stress parameters including glyoxalase I activity were measured. Results GSH supplementation with 2 mM N -acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) increased the viability, GSH level and the GSH-dependent glyoxalase I activity in 50 mM glucose-treated VL-17A cells. Further, pretreatment of 50 mM glucose-treated VL-17A cells with NAC or UDCA decreased oxidative stress (levels of reactive oxygen species and protein carbonylation), apoptosis (caspase 3 activity and annexin V–propidium iodide positive cells) and glutathionylated protein formation, a measure of oxidative stress. GSH depletion with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) potentiated the decrease in viability, glyoxalase I activity and increase in oxidative stress and apoptosis, with decreased GSH levels in 50 mM glucose-treated VL-17A cells. Conclusion Thus, changes in GSH levels with exogenous agents such as NAC, UDCA, BSO or DEM modulate hyperglycemia-mediated injury in a cell model of VL-17A liver cells.

Description: Purpose Platelet-activating factor (PAF), a potent inflammatory mediator, is implicated in atherosclerosis. Its key biosynthetic enzymes are lyso-PAF acetyltransferases (lyso-PAF-AT), responsible for PAF synthesis through the remodeling route and a specific CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), responsible for its de novo biosynthesis. PAF acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase A 2 catabolize PAF. The impact of diet on PAF metabolism is ill-defined. The aim was to investigate associations between PAF, its enzymes and dietary factors. Methods One-hundred and six ( n  = 106) healthy volunteers were recruited. Food-frequency questionnaires, dietary recalls, lifestyle and biochemical variables were collected. Food groups, macronutrient intake, a priori (MedDietScore) and a posteriori defined food patterns with PCA analysis, dietary antioxidant capacity (DAC), glycemic index (GI) and glycemic load were assessed. Results PAF was inversely correlated with antioxidant-rich foods (herbal drinks and coffee), the DAC as well as a dietary pattern characterized by legumes, vegetables, poultry and fish (all P s 〈 0.05). PAF was positively correlated to % fat intake. Lyso-PAF-AT was also negatively associated with healthy patterns (fruits, nuts and herbal drinks, and a pattern rich in olive oil and whole-wheat products), as well as the DAC and % monounsaturated fatty acids. PAF-CPT was negatively associated with GI and coffee intake and positively with dietary cholesterol. PAF-AH was negatively associated with coffee and positively associated with alcohol consumption (all P s 〈 0.05). Conclusions In conclusion, the DAC and healthy dietary patterns were inversely associated with PAF or its biosynthetic enzymes, suggesting potential new mechanisms of the diet–disease associations.

Description: Purpose Exercise induces oxidative stress and causes adaptations in antioxidant defenses. The aim of the present study was to determine the effects of a 2-month diet supplementation with docosahexaenoic acid (DHA) on the pro-oxidant and antioxidant status of peripheral blood mononuclear cells (PBMCs) during football training and after acute exercise. Methods Fifteen male football players, in a randomized double-blind trial, ingested a beverage enriched with DHA or a placebo for 8 weeks. Blood samples were collected in basal conditions before and after the training period and after an acute and intense exercise. Results The training season increased the carbonyl and nitrotyrosine index but decreased the malondialdehyde (MDA) levels. Basal catalase activity decreased in both groups after 8 weeks of training, whereas glutathione peroxidase activity increased mainly in the placebo group. Protein levels of uncoupling proteins (UCP2 and UCP3) and inducible nitric oxide synthase significantly increased after the training period. Acute exercise induced redistribution in the number of circulating cells, increased the MDA levels and nitrotyrosine index, and decreased the levels of nitrate. Acute exercise also increased PBMCs reactive oxygen species (ROS) production after immune stimulation. Diet supplementation with DHA significantly increased the UCP3 levels after training and the superoxide dismutase protein levels after acute exercise, and reduced the production of ROS after acute exercise. Conclusion Docosahexaenoic acid increased the antioxidant capabilities while reducing the mitochondrial ROS production in a regular football training period and reduced the oxidative damage markers in response to acute exercise.

Description: Purpose To study the effect of isoenergetic administration to adult rats of high-fat or high-fat–high-fructose diet for 2 weeks on skeletal muscle mitochondrial energetic. Methods Body and skeletal muscle composition, energy balance, plasma lipid profile and glucose tolerance were measured, together with mitochondrial functionality, oxidative stress and antioxidant defense. Results Rats fed high-fat–high-fructose diet exhibited significantly higher plasma triglycerides and non-esterified fatty acids, together with significantly higher plasma glucose and insulin response to glucose load. Skeletal muscle triglycerides and ceramide were significantly higher in rats fed high-fat–high-fructose diet. Skeletal muscle mitochondrial energetic efficiency and uncoupling protein 3 content were significantly higher, while adenine nucleotide translocase content was significantly lower, in rats fed high-fat or high-fat–high-fructose diet. Conclusions The results suggest that a high-fat–high-fructose diet even without hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial energetic efficiency, with two detrimental effects: (a) energy sparing that contributes to the early onset of obesity and (b) reduced oxidation of fatty acids and lipid accumulation in skeletal muscle, which could generate insulin resistance.

Description: Background Sister chromatid exchange (SCE) is a widely used sensitive cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results of human monitoring studies and cytogenetic damage have revealed that biological effects of genotoxic exposures are influenced by confounding factors related to life-style. Vegetable and fruit consumption may play a role, but available results are not consistent. The purpose of the study was to investigate the effect of consumption of raw and cooked vegetables and fruits on SCE frequency. Methods A total of 62 participants included colorectal cancer (CRC) patients, hospital-based controls and healthy laboratory workers. SCE frequency was assessed in blood lymphocytes. Frequency of vegetable and fruit consumption was gathered by structured semi-quantitative food frequency questionnaire. Results SCE frequency was lowest among hospital-based controls (4.4 ± 1.1), a bit higher in CRC patients (4.5 ± 1.0) and highest among laboratory workers (7.4 ± 1.2) ( p  〈 0.05). Multivariable linear regression showed a significant inverse effect ( b  = −0.20) of raw vegetable consumption, but not so for intake of cooked vegetables and fruits. Conclusions The results of the study have shown the beneficial effect of consumption of raw vegetables on disrupted replication of DNA measured by SCE frequency, implying protection against genotoxic agents. Further effort is required to verify the role of cooked vegetables and fruits.

Description: Background Amount and type of dietary protein have been shown to influence blood lipids. The present study aimed to evaluate the effects of a water-soluble fraction of chicken protein (CP) on plasma and hepatic lipid metabolism in normolipidemic rats. Methods Male Wistar rats were fed either a control diet with 20 % w/w casein as the protein source, or an experimental diet where casein was replaced with CP at 6, 14, or 20 % w/w for 4 weeks. Results Rats fed CP had markedly reduced levels of triacylglycerols (TAG) and cholesterol in both plasma and liver, accompanied by stimulated hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase 2 activity in the 20 % CP group compared to the control group. In addition, reduced activities and gene expression of hepatic enzymes involved in lipogenesis were observed. The gene expression of sterol regulatory element-binding transcription factor 1 was reduced in the 20 % CP-fed rats, whereas gene expression of peroxisome proliferator-activated receptor alpha was increased. Moreover, 6, 14, and 20 % CP-fed rats had significantly increased free carnitine and acylcarnitine plasma levels compared to control rats. The plasma methionine/glycine and lysine/arginine ratios were reduced in 20 % CP-treated rats. The mRNA level of ATP-binding cassette 4 was increased in the 20 % CP group, accompanied by the increased level of plasma bile acids. Conclusions The present data suggest that the hypotriglyceridemic property of a water-soluble fraction of CP is primarily due to effects on TAG synthesis and mitochondrial fatty acid oxidation. The cholesterol-lowering effect by CP may be linked to increased bile acid formation.

Description: Purpose Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells (WBC). However, effects on the level of spontaneous DNA strand breaks, a well established marker of health risk, have not been specifically reported yet. We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA strand breaks. Methods Healthy men ( n  = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks. The study coffee was a blend providing high amounts of both caffeoylquinic acids (10.18 ± 0.33 mg/g) and the roast product N -methylpyridinium (1.10 ± 0.05 mg/g). Before and after the coffee/water consumption phase, spontaneous strand breaks were determined by comet assay. Results At baseline, both groups exhibited a similar level of spontaneous DNA strand breaks. In the intervention phase, spontaneous DNA strand breaks slightly increased in the control (water only) group whereas they significantly decreased in the coffee group, leading to a 27 % difference within both arms ( p  = 0.0002). Food frequency questionnaires indicated no differences in the overall diet between groups, and mean body weight during the intervention phases remained stable. The consumption of the study coffee substantially lowered the level of spontaneous DNA strand breaks in WBC. Conclusion We conclude that regular coffee consumption contributes to DNA integrity.

Description: Purpose Childhood obesity is an increasing problem and is accompanied by metabolic disturbances. Recently, we have identified 14 serum metabolites by a metabolomics approach (FIA-MS/MS), which showed altered concentrations in obese children as compared to normal-weight children. Obese children demonstrated higher concentrations of two acylcarnitines and lower levels of three amino acids, six acyl–alkyl phosphatidylcholines, and three lysophosphatidylcholines. The aim of this study was to analyze whether these alterations normalize in weight loss. Methods We analyzed the changes of these 14 metabolites by the same metabolic kit as in our previous study in serum samples of 80 obese children with substantial weight loss (BMI-SDS reduction 〉0.5) and in 80 obese children with stable weight status all participating in a 1-year lifestyle intervention. Results In the children without weight change, no significant changes of metabolite concentrations could be observed. In children with substantial weight loss, glutamine, methionine, the lysophosphatidylcholines LPCaC18:1, LPCaC18:2, and LPCa20:4, as well as the acyl–alkyl phosphatidylcholine PCaeC36:2 increased significantly, while the acylcarnitines C12:1 and C16:1, proline, PCaeC34:1, PCaeC34:2, PCaeC34:3, PCaeC36:3, and PCaeC38:2 did not change significantly. Conclusions The changes of glutamine, methionine, LPCaC18:1, LPCaC18:2, LPCa20:4, and PCaeC36:2 seem to be related to the changes of dieting or exercise habits in lifestyle intervention or to be a consequence of overweight since they normalized in weight loss. Further studies should substantiate our findings.