European Journal of Nutrition (v.52, #6)

Antioxidant nutrients and age-related cognitive decline: a systematic review of population-based cohort studies by Snorri Bjorn Rafnsson; Vardis Dilis; Antonia Trichopoulou (1553-1567).
To further inform the debate on the possible cognitive benefits of antioxidant nutrients in the elderly, we systematically reviewed available prospective studies while paying a special attention to their methodological quality.This is a systematic review of studies involving major antioxidant nutrients and change in cognitive performance. Abstracts were independently reviewed; studies were selected based on prespecified criteria. Methodological quality of primary studies was assessed using a methodological checklist for cohort studies. Findings were presented using a narrative synthesis and tabulation of results.Eight-hundred and fifty potentially eligible studies were identified; 10 met the inclusion criteria and were retained for data extraction and appraisal. The main supportive evidence came from two studies, both judged to be of high quality: The first observed an accelerated decline in global cognition, attention, and psychomotor speed over 9 years, concomitant to a decrease in plasma selenium levels over the same period; the second study reported a slower rate of global cognitive decline over 3 years in persons in the highest quartile of intake of vitamins C, E, and carotenes. All associations persisted after adjustment for confounding factors. Evidence in favor of beneficial associations of higher dietary intake of vitamin E and flavonoids, as well as higher serum beta carotene levels, came from further studies of only adequate quality.There is a possibility for protective effects of antioxidant nutrients against decline in cognition in older people although the supportive evidence is still limited in number. This association deserves further examination in additional quality investigations.
Keywords: Antioxidants; Cognition; Elderly; Systematic review

Postprandial glucose, insulin and gastrointestinal hormones in healthy and diabetic subjects fed a fructose-free and resistant starch type IV-enriched enteral formula by Cruz Erika García-Rodríguez; María Dolores Mesa; Josune Olza; Gilda Buccianti; Milagros Pérez; Rosario Moreno-Torres; Antonio Pérez de la Cruz; Ángel Gil (1569-1578).
Reducing the dietary glycaemic response has been proposed as a means of reducing the risk of diabetes.To evaluate the effects of a new diabetes-specific formula (DSF) enriched with resistant starch type IV and fructose-free on postprandial glycaemia, insulinaemia and gastrointestinal hormones in healthy volunteers and in outpatient type 2 diabetics. (1) Twenty-four healthy volunteers were divided into two groups: Group 1 ( n = 10) was provided 50 g of the carbohydrate (CHO) constituent of the new product and 50 g of glucose separated by 1 week; Group 2 ( n = 14) was provided 400 ml of the new DSF (T-Diet Plus® Diabet NP) and 400 ml of a control product separated by 1 week. (2) Ten type 2 diabetic patients received 400 ml of the new DSF and two other commercially available DSF (Glucerna® SR and Novasource® Diabet) on three occasions separated by 1 week. Venous blood samples were drawn at time 0 and at different times until 120 min. Glucose, insulin and gastrointestinal hormones were determined. Glycaemic and insulinaemic indices and glycaemic load were calculated.The CHO constituent and the new DSF showed low glycaemic index and glycaemic load. In healthy subjects, insulin and C-peptide release were lower after administration of the CHO constituent as well as after the new DSF (P < 0.001). Ghrelin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) production were lower after intake of the CHO constituent (P ranging from <0.001 to 0.019) compared with glucose, and GIP was lower after ingestion of the new DSF (P = 0.002) than after the control product. In type 2 diabetic patients, glucose AUC was lower after the administration of the new DSF (P = 0.037) compared with the others.Our results indicate that this new product could be beneficial for diabetic patients.
Keywords: Enteral nutrition; Diabetes mellitus type 2; Carbohydrates; Insulin; Blood glucose; Gastrointestinal hormones

Capsaicin, the active ingredient of chilli, and medium-chain triglycerides (MCT) have been shown to increase diet-induced thermogenesis (DIT), improve satiety and decrease energy intake. Combinations of thermogenic ingredients have previously been investigated such as mustard and chilli, or capsaicin and green tea with positive effects. The aim of this study was to investigate the combined effects of chilli and MCT feeding on DIT and satiety in healthy volunteers.Seven healthy volunteers were tested on four occasions following an overnight fast. Volunteers were fed a breakfast containing chilli and MCT oil, chilli and sunflower oil, bell pepper and sunflower oil or bell pepper and MCT oil. Satiety and gastrointestinal comfort were measured using visual analogue scales (VAS) and category scales. Baseline energy expenditure, and DIT and fat oxidation were measured for 6 h using indirect calorimetry.There were significant differences in DIT between the meals (P = 0.003) which increased from 7.0 % for pepper–sunflower oil to 10.7 % for chilli–MCT oil. The predominant differences existed between the chilli–MCT oil and chilli–sunflower oil (P = 0.013), between chilli–MCT oil and pepper–sunflower oil (P = 0.007) and between pepper–sunflower oil and pepper–MCT oil (P = 0.004). There was a significant difference in fat oxidation between the pepper–sunflower oil and pepper–MCT oil (P = 0.032). There were no differences in any VAS satiety parameters or gastrointestinal comfort ratings.Adding chilli and MCT to meals increases DIT by over 50 % which over time may cumulate to help induce weight loss and prevent weight gain or regain.
Keywords: Chilli; Energy expenditure; Medium-chain triglyceride; Satiety; Diet-induced thermogenesis

Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity by Victoria Catalán; Javier Gómez-Ambrosi; Amaia Rodríguez; Beatriz Ramírez; Fernando Rotellar; Victor Valentí; Camilo Silva; María J. Gil; Javier Salvador; Gema Frühbeck (1587-1595).
Six-transmembrane epithelial antigen of prostate (STEAP)-4 and neutrophil gelatinase-associated lipocalin (NGAL) are novel adipokines related to iron homeostasis with potential roles in insulin resistance and inflammation. The aim of the present work was to evaluate the effect of obesity and iron status on gene expression levels of STEAP-4 and NGAL in visceral adipose tissue (VAT) and its implication in inflammation.VAT biopsies obtained from 53 subjects were used in the study. Real-time PCR and Western-blot were performed to quantify the levels of STEAP4 and NGAL in VAT as well as the association with other genes implicated in inflammatory pathways. Circulating ferritin and free iron concentrations were also determined.Obese patients exhibited significantly increased STEAP4 and NGAL mRNA expression levels (P < 0.001) compared to lean subjects. Protein expression levels of NGAL (P < 0.05) and STEAP4 were also higher in the visceral fat depot of obese patients, although protein levels of STEAP4 did not reach statistical significance. A negative correlation (P < 0.05) between free iron concentrations and gene expression levels of both STEAP4 and NGAL was found, while circulating ferritin concentrations were positively correlated (P < 0.05) with NGAL mRNA after body fat (BF) adjustment. Furthermore, a significant positive association between STEAP4 and NGAL gene expression levels with inflammatory markers was also detected (P < 0.01).These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.
Keywords: Iron homeostasis; Ferritin; Obesity; Inflammation; STAMP2; Lipocalin-2

Change in maternal body mass index is associated with offspring body mass index: a 21-year prospective study by Abdullah A. Mamun; Michael J. O’Callaghan; Gail M. Williams; Jake M. Najman (1597-1606).
To examine whether changes in maternal overweight and obesity from pre-pregnancy to two decades postpartum predict the body mass index (BMI) of adult offspring.We used a subsample of 1997 mother–offspring pairs from the 7,223 original cohorts of women who gave birth in Brisbane, Australia, between 1981 and 1984. Multiple linear regression and multinomial logistic regression were used to examine the relationship between change in maternal BMI from pre-pregnancy to 21-year postpartum, and offspring BMI at 21-year, adjusting for potential confounding factors.At 21-year postpartum, 31.15 % mothers were overweight and a further 30.80 % were obese. Mothers gained a mean weight of 16.07 kg over the 21 year. We found that the offspring of mothers who became overweight or remained overweight at 21-year postpartum were at greater risk of being overweight and obese at 21 years. In the adjusted model, offspring of mothers who had normal BMI before pregnancy but became overweight by 21-year postpartum were (odds ratio) 1.72 (95 % CI = 1.20, 2.47) times more likely to be overweight. Compared to offspring of mothers who maintained normal weight over two decades, offspring of mothers who remained persistently overweight were (odds ratio) 5.39 (95 % CI = 3.50, 8.30) times more likely to be obese by age 21 year.The findings of this study suggest that long-term changes in maternal BMI from pre-pregnancy to 21-year postpartum are independently associated with BMI in their young adult offspring.
Keywords: Maternal overweight; Offspring obesity; BMI change; Confounders

Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice by Myoung Jin Son; Miki Minakawa; Yutaka Miura; Kazumi Yagasaki (1607-1619).
Although several researches have demonstrated that rooibos extract has hypoglycemic effect, the role of aspalathin, a main polyphenol in the extract, remains unclear. Our aims were to find specific mechanisms for anti-diabetic action of aspalathin employing a rat skeletal muscle-derived cell line (L6 myocytes) and a rat-derived pancreatic β-cell line (RIN-5F cells) and to investigate its effect in type 2 diabetic model ob/ob mice.We investigated in vitro the effect of aspalathin on the glucose metabolism through the studies on molecular mechanisms of glucose uptake using cultured L6 myotubes. We also measured the antioxidative ability of aspalathin against reactive oxygen species (ROS) generated by artificial advanced glycation end product (AGE) in RIN-5F cells. In vivo, ob/ob mice were fed 0.1 % aspalathin-containing diet for 5 weeks, and the effect of aspalathin on fasting blood glucose level, glucose intolerance, and hepatic gene expression was studied.Aspalathin dose dependently increased glucose uptake by L6 myotubes and promoted AMP-activated protein kinase (AMPK) phosphorylation. Aspalathin enhanced GLUT4 translocation to plasma membrane in L6 myoblasts and myotubes. In RIN-5F cells, aspalathin suppressed AGE-induced rises in ROS. In vivo, aspalathin significantly suppressed the increase in fasting blood glucose levels and improved glucose intolerance. Furthermore, aspalathin decreased expression of hepatic genes related to gluconeogenesis and lipogenesis.Hypoglycemic effect of aspalathin is related to increased GLUT4 translocation to plasma membrane via AMPK activation. In addition, aspalathin reduces the gene expression of hepatic enzymes related to glucose production and lipogenesis. These results strongly suggest that aspalathin has anti-diabetic potential.
Keywords: Aspalathin; AMPK; GLUT4 translocation; Hyperglycemia; Advanced glycation end products (AGEs)

Inhibition of DNA-dependent protein kinase reduced palmitate and oleate-induced lipid accumulation in HepG2 cells by Hiu Yee Kwan; Wang Fun Fong; Zhijun Yang; Zhi-Ling Yu; Wen-Luan Wendy Hsiao (1621-1630).
The aim of this study is to investigate the involvement of DNA-dependent protein kinase (DNA-PK) in palmitate and oleate-induced lipid accumulation in hepatocytes.We treated HepG2 with free fatty acids (FFA) (0.33 mM palmitate and 0.66 mM oleate) mixture to induce lipid accumulation. Cellular lipid was determined by Nile Red staining followed by flow cytometry detection as well as phase contrast and fluorescence microscope examination. Cell viability was detected by MTT assay. Apoptosis was detected by DAPI staining. Lipogenic gene expression was examined by real-time PCR at mRNA level and Western blotting at protein level. Promoter transcriptional activity was measured by dual luciferase assay.FFA treatment neither affected HepG2 cells viability nor induced DNA fragmentation, while induced cellular lipid accumulation was associated by the upregulation of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FAS) at both mRNA and protein levels. Interestingly, we also found that both the protein phosphatase 2A (PP2A) protein expression and DNA-PK activity were increased in these cells. Inhibition of PP2A by okadaic acid, knockdown of DNA-PK by siRNA or inhibition of DNA-PK by specific DNA-PK inhibitors curtailed the FFA-induced upregulations of the SREBP1 mRNA expression and the nuclear active SREBP1 protein expression, and reduced FFA-induced upregulation of FAS promoter transcriptional activity and lipid accumulation.This is the first time suggesting that inhibition of DNA-PK reduced FFA-induced lipid accumulation in hepatocytes. This finding might help us better understand non-alcoholic steatohepatitis pathogenesis.
Keywords: DNA-PK; PP2A; Palmitate; Oleate; Lipid; Hepatocellular steatosis

Predictors of haemoconcentration at delivery: association with low birth weight by N. Aranda; B. Ribot; F. Viteri; P. Cavallé; V. Arija (1631-1639).
To assess the factors associated with risk of haemoconcentration at delivery, such as initial haemoglobin levels and alterations in the HFE gene, and its effect on low birth weight in pregnant women supplemented with moderate doses of iron.Case–control study nested in a longitudinal study conducted on 217 healthy pregnant women taking moderate iron supplementation and their newborns. Women were classified according to the risk of haemoconcentration at delivery, defined as Hb > 130 g/L. Each subject’s obstetric and clinical history, smoking habit, and iron biochemical parameters (haemoglobin (Hb), serum ferritin and transferrin saturation) were recorded at 1st, 2nd and 3rd trimester and at delivery. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were also measured.The average of iron supplementation of all the women was 43.9 mg/dia (geometric mean, 95 % CI: 43.6–44.1). Higher levels of Hb at early gestation and the presence of HFE mutations were associated with greater risk of haemoconcentration at delivery, adjusted odds ratios of 1.14 (95 % CI: 1.05–1.25) and 5.35 (95 % CI: 1.6–17.8). Haemoconcentration at delivery was associated with a greater risk of low birth weight, adjusted odd ratio of 11.48 (95 % CI: 1.13–116.6).Moderate daily doses of supplementary iron may be harmful for foetal growth in women with alterations in HFE gene and who started pregnancy with good haemoglobin levels. Overall, this suggests the importance of determining a woman’s iron status early in her pregnancy in order to establish a more appropriate pattern of supplementation.
Keywords: Pregnancy; Haemoconcentration; Iron status; Iron supplementation; HFE mutations; Low birth weight

Serum leptin and total dietary energy intake: the INTERLIPID Study by Yasuyuki Nakamura; Hirotsugu Ueshima; Nagako Okuda; Yoshitaka Murakami; Katsuyuki Miura; Yoshikuni Kita; Tomonori Okamura; Akira Okayama; Tanvir C. Turin; Sohel R. Choudhry; Beatriz Rodriguez; J. David Curb; Jeremiah Stamler (1641-1648).
It has been hypothesized that leptin-induced appetite suppression is impaired in obese individuals, but little human evidence is available documenting this. We investigated relations between serum leptin and total energy intake using INTERLIPID/INTERMAP data on Japanese–Americans in Hawaii and Japanese in Japan.Serum leptin and nutrient intakes were examined by standardized methods in men and women aged 40–59 years from two population samples, one Japanese–American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression analyses stratified by BMI category (<25 kg/m2, 25–29.9 kg/m2, and ≥30 kg/m2) with adjustment for possible confounders were used to examine the relation between log-leptin and total dietary energy intake.In multivariate regression analyses, in those with BMI < 25 kg/m2 and in those with BMI between 25 and 29.9 kg/m2, log-leptin was not significantly related to total dietary energy intake; in those with BMI ≥ 30 kg/m2, it was significantly inversely related to total dietary energy intake (P = 0.029), independent of body weight and physical activity. Physical activity score was significantly positively related to total dietary energy intake only in participants with BMI < 25 kg/m2 (P < 0.001).Leptin was significantly inversely associated with dietary energy intake in obese persons, but not in overweight and normal-weight persons.
Keywords: Leptin; Japanese in Japan and Hawaii; Obesity; Body mass; Total energy intake; Population study

The renoprotective effect of l-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression by Sonia Zambrano; Antonio Jesús Blanca; María Victoria Ruiz-Armenta; José Luis Miguel-Carrasco; Elisa Revilla; Consuelo Santa-María; Alfonso Mate; Carmen María Vázquez (1649-1659).
Arterial hypertension is associated with a high production of reactive oxygen species and a decrease in the antioxidant defense systems. Based on the lack of toxicity of l-carnitine (LC) and previous studies reporting beneficial effects of this compound in experimental models of hypertension, the aim of this work was to test the hypothesis that LC might protect the kidney against hypertension-induced oxidative damage, as well as to investigate the mechanisms involved in this effect. To this end, specific activities and protein/mRNA expression of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, and superoxide dismutase), and those of NADPH oxidase (the main responsible for superoxide anion production in renal tissue) have been measured in renal cortex homogenates from NG-nitro-l-arginine methyl ester (L-NAME)-treated rats and control normotensive rats. In addition, components of the renin–angiotensin system (RAS) and redox-sensitive transcription factors (NF-κB, Nrf2, and PPARα) have also been evaluated.Male Wistar rats aged 6–8 weeks were divided into four groups of six animals each: (1) control, normotensive Wistar rats (with free access to tap water); (2) Wistar rats subjected to treatment with 25 mg of L-NAME/kg body weight/day dissolved in the drinking water, in order to develop L-NAME-induced hypertension; (3) Wistar rats subjected to treatment with 400 mg of LC/kg body weight/day (also dissolved in the drinking water); and (4) L-NAME-treated rats subjected to simultaneous treatment with LC at the indicated doses.The beneficial effect of LC supplementation on oxidative damage in the renal cortex of hypertensive rats reversed hypertension-associated renal function damage and produced an upregulation of both antioxidant enzymes and eNOS, and with a downregulation of both NADPH oxidase and RAS components. LC improves the oxidative stress response through a specific modulation of NF-κB, Nrf2, and PPARα transcription factors. Thus, the low production of superoxide anions, subsequent to NADPH oxidase inhibition, might act by increasing the expression of Nrf2 and PPARα and by decreasing that of NF-κB, which, in turn, would enhance the antioxidant defense systems.Our results might support the use of LC to prevent hypertension-induced renal damage.
Keywords: Hypertension; Kidney; l-carnitine; L-NAME; Nitric oxide; Oxidative stress; Renin–angiotensin system

Iron status of one-year-olds and association with breast milk, cow’s milk or formula in late infancy by Asa V. Thorisdottir; Alfons Ramel; Gestur I. Palsson; Helgi Tomassson; Inga Thorsdottir (1661-1668).
Studies on iron status in infancy and early childhood have shown contradicting results concerning prolonged breast-feeding and cow’s milk intake. The aim of the present study was to investigate associations between iron status among one-year-olds and feeding, with focus on the type of milk.Randomly selected healthy infants were prospectively investigated until 1 year of age in two cohorts born 1995–1996 (n = 114) and 2005 (n = 140). Information on birth data, feeding and growth until 12 months and iron status at 12 months was collected. Data from the two cohorts were pooled and the infants categorized into three groups according to their predominant milk consumption at 9 months of age, that is, breast milk, cow’s milk or follow-on formula.The prevalence of iron deficiency was highest in the cow’s milk group and lowest in the follow-on formula group. According to a linear model, adjusted for gender, birth weight and exclusive breast-feeding duration, cow’s milk consumption was negatively associated with serum ferritin (SF) and formula positively, but breast milk not. Predicted SF (μg/l) = 11.652(intercept) − 5.362(boy) + 0.005 × birth weight (g) + 2.826(exclusively breastfed ≥ 4 months) + 0.027 × formula (ml) − 0.022 × cow’s milk (ml) + 0.005 × breast milk (ml). Correction for other dietary factors did not change these results.In this pooled analysis, cow’s milk intake in late infancy associated negatively, and follow-on formula positively, with iron status. Prolonged partial breast-feeding does not seem to be of importance for iron status. Fortified food seems to improve iron status in late infancy.
Keywords: Iron status; Infant nutrition; Follow-on formula; Breast milk; Cow’s milk; Late infancy

Comparative in vitro inhibition of urinary tract pathogens by single- and multi-strain probiotics by C. M. C. Chapman; G. R. Gibson; S. Todd; I. Rowland (1669-1677).
Multi-species probiotic preparations have been suggested as having a wide spectrum of application, although few studies have compared their efficacy with that of individual component strains at equal concentrations. We therefore tested the ability of 4 single probiotics and 4 probiotic mixtures to inhibit the urinary tract pathogens Escherichia coli NCTC 9001 and Enterococcus faecalis NCTC 00775.We used an agar spot test to test the ability of viable cells to inhibit pathogens, while a broth inhibition assay was used to assess inhibition by cell-free probiotic supernatants in both pH-neutralised and non-neutralised forms.In the agar spot test, all probiotic treatments showed inhibition, L. acidophilus was the most inhibitory single strain against E. faecalis, L. fermentum the most inhibitory against E. coli. A commercially available mixture of 14 strains (Bio-Kult®) was the most effective mixture, against E. faecalis, the 3-lactobacillus mixture the most inhibitory against E. coli. Mixtures were not significantly more inhibitory than single strains. In the broth inhibition assays, all probiotic supernatants inhibited both pathogens when pH was not controlled, with only 2 treatments causing inhibition at a neutral pH.Both viable cells of probiotics and supernatants of probiotic cultures were able to inhibit growth of two urinary tract pathogens. Probiotic mixtures prevented the growth of urinary tract pathogens but were not significantly more inhibitory than single strains. Probiotics appear to produce metabolites that are inhibitory towards urinary tract pathogens. Probiotics display potential to reduce the incidence of urinary tract infections via inhibition of colonisation.
Keywords: Probiotic; Multi-species; Urinary; Pathogen

The usefulness of anthropometric measures by Francesco Landi; Rosa Liperoti; Graziano Onder (1683-1683).