European Journal of Nutrition (v.52, #1)

Nutrient reference values for bioactives: new approaches needed? A conference report by Hans Konrad Biesalski; John W. Erdman Jr.; John Hathcock; Kathleen Ellwood; Stephen Beatty; Elizabeth Johnson; Roberto Marchioli; Lotte Lauritzen; Harry B. Rice; Andrew Shao; James C. Griffiths (1-9).
Nutrients can be classified as either “essential” or “non-essential,” the latter are also termed bioactive substances. Whereas the absence of essential nutrients from the diet results in overt deficiency often times with moderate to severe physiological decrements, the absence of bioactive substances from the diet results in suboptimal health. Nutrient reference values are set by Codex Alimentarius and regulatory bodies in many countries, mostly for essential nutrients with recommended daily intakes. The IOM in the United States has defined a set of four DRIs that, when data are appropriate, include an EAR, a RDA that is derived from the EAR, an AI for nutrients without appropriate data to identify an EAR, and an UL. From the RDA, the United States derives a labeling value called the DV, which applies to older children and most adults. In Codex, the equivalents of the DVs are the NRVs to be used in calculating percentage values on food labels. Nothing in the IOM documents specifies that labeling values can be set only for what have been defined to date as essential nutrients. Indeed, the US Food and Drug Administration sets a labeling value for dietary fiber based on the IOM AI for this ingredient. This conference explores the definitions, concepts, and data on two of the best examples of bioactive substances that, perhaps, should have NRVs: lutein and zeaxanthin, and n-3 long-chain polyunsaturated fatty acids.
Keywords: Nutrient reference values; Non-essential nutrients; Adequate intake; Lutein; Zeaxanthin; Meso-zeaxanthin; n-3 Long-chain polyunsaturated fatty acids

To comprehensively review the data on the relationship between the consumption of dairy fat and high-fat dairy foods, obesity, and cardiometabolic disease.We have conducted a systematic literature review of observational studies on the relationship between dairy fat and high-fat dairy foods, obesity, and cardiometabolic disease. We have integrated these findings with data from controlled studies showing effects of several minor dairy fatty acids on adiposity and cardiometabolic risk factors, and data on how bovine feeding practices influence the composition of dairy fat.In 11 of 16 studies, high-fat dairy intake was inversely associated with measures of adiposity. Studies examining the relationship between high-fat dairy consumption and metabolic health reported either an inverse or no association. Studies investigating the connection between high-fat dairy intake and diabetes or cardiovascular disease incidence were inconsistent. We discuss factors that may have contributed to the variability between studies, including differences in (1) the potential for residual confounding; (2) the types of high-fat dairy foods consumed; and (3) bovine feeding practices (pasture- vs. grain-based) known to influence the composition of dairy fat.The observational evidence does not support the hypothesis that dairy fat or high-fat dairy foods contribute to obesity or cardiometabolic risk, and suggests that high-fat dairy consumption within typical dietary patterns is inversely associated with obesity risk. Although not conclusive, these findings may provide a rationale for future research into the bioactive properties of dairy fat and the impact of bovine feeding practices on the health effects of dairy fat.
Keywords: Milk fat; Dairy fat; Obesity; Adiposity; Diabetes; Cardiovascular disease

Nutritional factors is one of the most important regulators in the progression of cancer. Some dietary elements promote the growth of cancer but others, such as plant-derived compounds, may reverse this process.We tried to investigate yet another approach of cancer prevention through cancer cell differentiation, using a common non-mutagenic flavonoid apigenin 7-glucoside.HL-60 cells were treated with or without apigenin 7-glucoside. Cell proliferation was measured by MTT assay, and the cell cycle distribution was estimated by propidium iodide staining of DNA. To determine cellular differentiation, cell surface differentiation markers CD11b and CD14 were used. Two-dimensional gel electrophoresis was then performed to identify proteins that may be important in HL-60 cell differentiation following apigenin 7-glucoside treatment.Apigenin 7-glucoside inhibited HL-60 cell growth, dose- and time-dependently, but did not cause apoptosis. The distribution of cells at different stages in the cell cycle indicated an accumulation of treated cells in G2/M phase. Moreover, apigenin 7-glucoside induced granulocytic differentiation of HL-60 cells. Ten proteins that might play essential role in granulocytic differentiation were identified by proteomics.A complete understanding of the preventive effects of plant-based diet on cancer depends on the mechanisms of action of different plant components on processes. We hope these findings may contribute to the understandings of the different approaches for chemoprevention of cancer.
Keywords: Differentiation; Proteomics; Apigenin 7-glucoside; HL-60 cells; Granulocyte

Adherence to Mediterranean diet and close dietetic supervision increase total dietary antioxidant intake and plasma antioxidant capacity in subjects with abdominal obesity by Anastasia I. Kolomvotsou; Loukianos S. Rallidis; Konstantinos C. Mountzouris; John Lekakis; Antonis Koutelidakis; Stamatis Efstathiou; Maria Nana-Anastasiou; Antonis Zampelas (37-48).
To determine the effect of Mediterranean-type diet and close dietetic supervision on dietary antioxidant intake and plasma total antioxidant capacity (TAC) in patients with abdominal obesity.Ninety subjects with abdominal obesity, 46 in intervention group, 44 in control group, participated in a 2-month, randomized, parallel dietary intervention. All participants were counseled on Greek Mediterranean diet. The intervention group was under close dietetic supervision, followed a specific relevant daily and weekly food plan consuming antioxidant-rich foods and food products. Total dietary antioxidant intake was calculated from the volunteers’ food diaries, and plasma TAC using plasma ORAC assay and plasma ferric-reducing antioxidant power (FRAP) assay, both at baseline and at 2 months.Following the 2-month period, total dietary antioxidant intake was increased in the intervention group compared to the control group (P = 0.000). In addition, increased intake of total fat, due to higher consumption of monounsaturated fatty acids, as well as increased intakes of dietary fiber, vitamin C and alcohol was also observed in the intervention group compared to the control group (P < 0.05). Plasma TAC was increased in the intervention group compared to the control group (P = 0.039) using the ORAC assay, while there was a trend toward a TAC increase (P = 0.077) using the FRAP assay.Adherence to a Mediterranean-type diet, with emphasis on an increase in foods rich in antioxidants and close dietetic supervision, can increase total dietary antioxidant intake and plasma TAC in patients with abdominal obesity.
Keywords: Obesity; ORAC; FRAP; Antioxidants; Mediterranean diet

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women by Nina Emaus; Nguyen D. Nguyen; Bjørg Almaas; Gro K. Berntsen; Jacqueline R. Center; Monika Christensen; Clara G. Gjesdal; Anne S. Grimsgaard; Tuan V. Nguyen; Laila Salomonsen; John A. Eisman; Vinjar M. Fønnebø (49-55).
Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women.The data reported here come from the enrolment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1–5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables.The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site.Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.
Keywords: Vitamin K; Under-carboxylated osteocalcin; Bone mineral density; Menopause

Waist-to-height ratio, waist circumference, and body mass index as indices of cardiometabolic risk among 36,642 Taiwanese adults by Wen-Cheng Li; I-Chuan Chen; Yu-Che Chang; Song-Seng Loke; Shih-Hao Wang; Kuang-Yu Hsiao (57-65).
We aimed to investigate the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with cardiometabolic risk.In this cross-sectional study, 21,038 men and 15,604 women who participated in a health check-up were included.In both men and women, the area under the curve (AUC) of WHtR was significantly greater than that of BMI or WC in the prediction of diabetes, hypertension, high total cholesterol, high triglycerides, and low HDL-cholesterol (P < 0.05 for all). The AUC for WHtR in the prediction of metabolic syndrome (MS) was also highest in the women (P < 0.05). After adjustment for potential confounders, the odds ratios and 95% confidence intervals for MS for each standard deviation increase in BMI, WHtR, and WC were 1.47 (1.46–1.49), 1.32 (1.31–1.33), and 1.19 (1.18–1.19), respectively. Finally, patients of either sex with a normal BMI or WC level, but with an elevated WHtR, had higher levels of various cardiometabolic risk factors in comparison with their normal BMI or WC, but low WHtR, counterparts (P < 0.05 for all).Among Taiwanese adults, a WHtR greater than 0.5 is a simple, yet effective indicator of centralized obesity and associated cardiometabolic risk, even among individuals deemed ‘healthy’ according to BMI and WC.
Keywords: Waist-to-height ratio; Waist circumference; Obesity; Diabetes; Body mass index; Asian

The risk of metabolic syndrome (MetS) is assessed based on the presence of risk factors that include dyslipidemia, hyperglycemia, hypertension and obesity. In this study, we assessed the risk of MetS using principle component (PC) analysis of MetS diagnostic parameters and examined whether the resulting eigenvalues are associated with the circulating concentrations of inflammatory cytokines [interleukin (IL)-1β and IL-6] and a marker for insulin sensitivity (adiponectin) in middle-aged Japanese men without treatment for metabolic diseases.We conducted a cross-sectional study of 308 Japanese men without treatment for metabolic diseases aged 40–69 years who participated in health checkups in Japan. We calculated the PC1 score from the following MetS diagnostic parameters: body mass index (BMI), fasting blood glucose, diastolic blood pressure, triacylglycerol and high-density lipoprotein cholesterol. We compared the relationship between PC1 scores and other clinical parameters, including IL-1β, IL-6 and adiponectin, by Spearman’s rank correlation coefficient analyses and Jonckheere–Terpstra test.The associations for most clinical parameters were higher with the PC1 score than with other MetS diagnostic parameters. Homeostasis model assessment–insulin resistance, an index of insulin resistance, showed stronger associations with PC1 score than with MetS diagnostic parameters. Significant associations for IL-1β, IL-6 and adiponectin were observed with the PC1 score, BMI and triacylglycerol; these associations were higher with the PC1 score than with BMI and triacylglycerol.The present results show that the PC1 score is closely associated with parameters of MetS, inflammation and insulin resistance.
Keywords: MetS; Principal component analysis; Inflammation; Insulin resistance; Japanese men without treatment for metabolic diseases

Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis by Prabukumar Anitha; Ramamurthi Vidya Priyadarsini; Krishnamurthy Kavitha; Paranthaman Thiyagarajan; Siddavaram Nagini (75-84).
Constitutive activation of the Wnt signaling pathway and its downstream effectors plays a key role in neoplastic transformation. The objective of this study was to investigate the effect of ellagic acid, a plant-derived polyphenol on Wnt/β-catenin signaling and its downstream circuits- NF-κB and mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.Hamsters were divided into six groups. The right buccal pouches of animals in groups 1–4 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 2–4 received in addition basal diet containing ellagic acid at a concentration of 0.1, 0.2, and 0.4% in the diet. Group 5 animals were given 0.4% ellagic acid alone. Group 6 animals served as control. The expression of the members of Wnt and NF-κB signaling and intrinsic apoptosis was evaluated by western blot analysis.Dietary supplementation of 0.4% ellagic acid suppressed the development of HBP carcinomas by preventing the constitutive activation of Wnt pathway through the downregulation of Fz, Dvl-2, GSK-3β and nuclear translocation of β-catenin. Abrogation of Wnt signaling by ellagic acid was also associated with inactivation of NF-κB and modulation of key components of the mitochondrial apoptotic network.Our findings suggest a functional crosstalk between Wnt and NF-κB signaling pathways in HBP carcinomas that is blocked by ellagic acid supplementation. Dietary ellagic acid that targets the Wnt/β-catenin pathway as well as its downstream signaling mediators is a unique candidate for cancer chemoprevention.
Keywords: Apoptosis; Chemoprevention; Ellagic acid; Hamster buccal pouch; NF-κB; Wnt

Anti-angiogenic properties of carnosol and carnosic acid, two major dietary compounds from rosemary by Auxiliadora López-Jiménez; Melissa García-Caballero; Miguel Ángel Medina; Ana R. Quesada (85-95).
The use of rosemary (Rosmarinus officinalis) leaves and their constituents as a source of dietary antioxidants and flavoring agents is continuously growing. Carnosol and carnosic acid, two major components of rosemary extracts, have shown activity for cancer prevention and therapy.In this study, we investigate the cytotoxic and anti-angiogenic activities of carnosol and carnosic acid, in order to get further insight into their mechanism of action.Our results demonstrate that the mentioned diterpenes inhibit certain functions of endothelial cells, namely, differentiation, proliferation, migration and proteolytic capability. Our data indicate that their growth inhibitory effect, exerted on proliferative endothelial and tumor cells, could be due to, at least in part, an induction of apoptosis. Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallantoic membrane assay.The anti-angiogenic activity of carnosol and carnosic acid could contribute to the chemopreventive, antitumoral and antimetastatic activities of rosemary extracts and suggests their potential in the treatment of other angiogenesis-related malignancies.
Keywords: Angiogenesis; Carnosic acid; Carnosol; Rosemary; Chemoprevention

Association between dietary patterns and the risk of metabolic syndrome among Lebanese adults by F. Naja; L. Nasreddine; L. Itani; N. Adra; A. M. Sibai; N. Hwalla (97-105).
The main objective of this study was to evaluate the association between dietary patterns and the metabolic syndrome (MetS) and its metabolic abnormalities among Lebanese adults, using data from a national nutrition survey.A cross-sectional analysis involving adults aged ≥18 years (n = 323) with no prior history of chronic diseases was conducted. Participants completed a brief sociodemographic and 61-item food frequency questionnaire. Anthropometric measurements and fasting blood samples were also obtained. The International Diabetes Federation criteria were used to classify study participants with the metabolic syndrome. Dietary patterns were identified by factor analysis. Multivariate logistic regression analysis was used to evaluate the associations of extracted patterns with MetS and its metabolic abnormalities.Out of 323 participants, 112 (34.6%) were classified as having MetS. Three dietary patterns were identified: “Fast Food/Dessert,” “Traditional Lebanese,” and “High Protein.” Compared with participants in the lowest quintile of the Fast Food/Dessert pattern, those in the highest quintile had significantly higher odds for MetS (OR, 3.13; 95% CI: 1.36–7.22) and hyperglycemia (OR, 3.81; 95% CI: 159–9.14). Subjects with the highest intake of the High Protein pattern had an increased risk for hypertension (OR, 2.98; 95% CI: 1.26–7.02). The Traditional Lebanese pattern showed no association with MetS or its components.The findings of this study demonstrate a positive association of the Fast Food/Dessert pattern with MetS and hyperglycemia among Lebanese adults. These results may guide the development of improved preventive nutrition interventions in this adult population.
Keywords: Dietary pattern; Factor analysis; Metabolic syndrome; Lebanon

Phytochemical composition of “mountain tea” from Sideritis clandestina subsp. clandestina and evaluation of its behavioral and oxidant/antioxidant effects on adult mice by Catherine G. Vasilopoulou; Vassiliki G. Kontogianni; Zacharoula I. Linardaki; Gregoris Iatrou; Fotini N. Lamari; Alexandra A. Nerantzaki; Ioannis P. Gerothanassis; Andreas G. Tzakos; Marigoula Margarity (107-116).
The goals of this study were to monitor the effect of drinking of herbal tea from Sideritis clandestina subsp. clandestina for 6 weeks on behavioral and oxidant/antioxidant parameters of adult male mice and also to evaluate its phytochemical composition.The phytochemical profile of the Sideritis tea was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface. The effects of two doses of the herbal infusion (2 and 4% w/v, daily) intake on anxiety-like state in mice were studied by the assessment of their thigmotactic behavior. The oxidant/antioxidant status of brain (-Ce), liver and heart of adult male Balb-c mice following the consumption of Sideritis tea was also evaluated via the measurement of malondialdehyde (MDA) and reduced glutathione (GSH) levels using fluorometric assays. Our study was further extended to determine the antioxidant effects of the herbal tea on specific brain regions (cerebral cortex, cerebellum and midbrain).The identified compounds were classified into several natural product classes: quinic acid derivatives, iridoids, phenylethanol glycosides and flavonoids. Our results showed that only the 4% Sideritis tea exhibited anxiolytic-like properties as evidenced by statistically significant (p < 0.05) decrease in the thigmotaxis time and increase in the number of entries to the central zone in comparison with the control group. Consumption of both tea doses (2 and 4% w/v) elevated GSH (12 and 28%, respectively, p < 0.05) and decreased MDA (16 and 29%, p < 0.05) levels in brain (-Ce), while liver and heart remained unaffected. In regard to the effect of herbal tea drinking (2 and 4% w/v) on specific brain regions, it caused a significant increase in GSH of cerebellum (13 and 36%, respectively, p < 0.05) and midbrain (17 and 36%, p < 0.05). Similarly, MDA levels were decreased in cerebellum (45 and 79%, respectively, p < 0.05) and midbrain (50 and 63%, respectively, p < 0.05), whereas cerebral cortex remained unaffected.Mountain tea drinking prevents anxiety-related behaviors and confers antioxidant protection to rodent’s tissues in a region-specific, dose-dependent manner, and its phytochemical constituents are shown for the first time.
Keywords: LC-MS/MS; Mountain tea; Sideritis clandestina subsp. clandestina ; Oxidant/antioxidant parameters; Thigmotaxis test

The aim of this study was to evaluate the dietary intake of energy and nutrients (DIEN) of Czech pregnant women and to assess relationships with body size variables during pregnancy.One hundred and fifty-two randomly recruited healthy pregnant Czech women, who were normoglycemic, euthyroid, nonsmokers, not anemic, and not users of chronic medications or abusers of alcohol or drugs from countryside and city with different education, were recruited for the study. Anthropometric parameters were measured and resting energy expenditure obtained by indirect calorimetry after 12 h of fasting during four phases of pregnancy. DIEN was evaluated from self-reported dietary intake records over 7 days.Positive correlations were demonstrated between measured resting energy expenditure and intake of energy, substrates and some minerals and vitamins, and negative correlations between DIEN and anthropometric parameters. Lower dietary intake of energy and differences between dietary intake of nutrients and recommended daily allowances during pregnancy of Czech women were documented.The difference between pregnancy body weight and ideal body weight was shown to be a determinant of DIEN. From recent knowledge on prevention of various pathological states, the supplementation or modification of nutritional intake of food with folate, iron, vitamin D, zinc, iodine and fiber for Czech pregnant women is recommended.
Keywords: Nutrition; Resting energy expenditure; Pregnancy

Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet by Kang Uk Yun; Chang Seon Ryu; Jung Min Oh; Chung Hyun Kim; Kye Sook Lee; Chul-Ho Lee; Hyun-Sun Lee; Bong-Hee Kim; Sang Kyum Kim (127-134).
Obesity, a feature of metabolic syndrome, is a risk factor for cardiovascular disease, and elevated plasma homocysteine is associated with increased cardiovascular risk. However, little published information is available concerning the effect of obesity on homocysteine metabolism.Hepatic homocysteine metabolism was determined in male C57BL/6 mice fed a high-fat diet for 12 weeks.High-fat diet increased plasma homocysteine but decreased hepatic homocysteine levels. Hepatic S-adenosylhomocysteine hydrolase levels were down-regulated in the obese mice, which was in part responsible for the decrease in hepatic S-adenosylmethionine/S-adenosylhomocysteine, which served as an index of transmethylation potential. Despite the decrease in hepatic cysteine, hepatic taurine synthesis was activated via up-regulation of cysteine dioxygenase. Hepatic levels of methionine adenosyltransferase I/III, methionine synthase, methylene tetrahydrofolate reductase, and gamma-glutamylcysteine ligase catalytic subunit were unchanged. Obese mice showed elevated betaine-homocysteine methyltransferase and decreased cystathionine beta-synthase activities, although the quantities of these enzymes were unchanged.This study suggests that plasma homocysteine level is increased in obesity-associated hepatic steatosis, possibly as a result of increased hepatic homocysteine efflux along with an altered sulfur amino acid metabolism.
Keywords: Homocysteine; Sulfur amino acid metabolism; High-fat diet; Hepatic steatosis; Obesity

Regulation of iron metabolism in Hamp/ mice in response to iron-deficient diet by Patarabutr Masaratana; Neeta Patel; Gladys O. Latunde-Dada; Sophie Vaulont; Robert J. Simpson; Andrew T. McKie (135-143).
Hepcidin, the liver-secreted iron regulatory peptide, maintains systemic iron homeostasis in response to several stimuli including dietary iron levels and body iron status. In addition, iron metabolism is controlled by several local regulatory mechanisms including IRP and Hif-2α activities independently of hepcidin. However, the roles of these mechanisms and their interaction particularly in hepcidin-deficient individuals are not yet fully understood. We, therefore, aimed to explore whether Hamp disruption affects iron homeostatic responses to dietary iron deficiency. Hepcidin1 knockout (Hamp/) mice and heterozygous littermates were fed with control or iron-deficient diet for 2 weeks. The expression of iron-related genes and proteins were determined by quantitative PCR and Western blot, respectively.Two-week iron-deficient diet feeding in Hamp/ mice did not alter serum iron but significantly reduced liver non-heme iron levels. This was also associated with increased ferroportin protein expression in the duodenum and spleen, whereas decreased expression was found in the liver. In addition, significant inductive effects of iron-deficient diet on Dcytb and DMT1 mRNA expression in the duodenum were noted with more pronounced effects in Hamp/ mice compared with controls. Hamp/ mice exhibited a more dramatic increase in the expression of iron transport machinery, which may be responsible for the unaltered serum iron levels upon iron-deficient diet feeding in these mice. Despite the lack of hepcidin, Hamp/ mice can maintain a degree of iron homeostasis in response to altered dietary iron through several hepcidin-independent mechanisms.
Keywords: Iron; Hepcidin; Iron deficiency; Hamp/ mice; Ferroportin

Relationship between the body adiposity index and cardiometabolic risk factors in obese postmenopausal women by Belinda Elisha; Rémi Rabasa-Lhoret; Virginie Messier; Joseph Abdulnour; Antony D. Karelis (145-151).
The purpose of the present secondary analysis study was to investigate the ability of the body adiposity index (BAI) to detect changes in % body fat levels before and after a weight loss intervention when compared to % body fat levels measured using dual-energy X-ray absorptiometry (DXA) and to examine the relationship between the BAI with cardiometabolic risk factors.The study population for this secondary analysis included 132 non-diabetic obese sedentary postmenopausal women (age: 57.2 ± 4.7 years, BMI: 35.0 ± 3.7 kg/m2) participating in a weight loss intervention that consisted of a calorie-restricted diet with or without resistance training. We measured: (1) visceral fat using CT-scan, (2) body composition using DXA, (3) hip circumference and height from which the BAI was calculated, and (4) cardiometabolic risk factors such as insulin sensitivity (using the hyperinsulinemic-euglycemic clamp), blood pressure as well as fasting plasma lipids, hsC-reactive protein (CRP), leptin, and glucose.Percent body fat levels for both methods significantly decreased after the weight loss intervention. In addition, the percent change in % body fat levels after the weight loss intervention was significantly different between % body fat measured using the DXA and the BAI (−4.5 ± 6.6 vs. −5.8 ± 5.9%; p = 0.03, respectively). However, we observed a good overall agreement between the two methods, as shown by the Bland–Altman analysis, for percent change in % body fat. Furthermore, similar correlations were observed between both measures of % body fat with cardiometabolic risk factors. However, results from the multiple linear regression analysis showed that % body fat using the BAI appeared to predict cardiometabolic risk factors differently than % body fat using the DXA in our cohort.Estimating % body fat using the BAI seems to accurately trace variations of % body fat after weight loss. However, this index showed differences in predicting cardiometabolic risk factors when compared to % body fat measured using DXA.
Keywords: Obesity; % body fat; Hip circumference and DXA

The effect of plant sterols on serum triglyceride concentrations is dependent on baseline concentrations: a pooled analysis of 12 randomised controlled trials by Isabelle Demonty; Rouyanne T. Ras; Henk C. M. van der Knaap; Linsie Meijer; Peter L. Zock; Johanna M. Geleijnse; Elke A. Trautwein (153-160).
Plant sterols (PS) are well known for their low-density lipoprotein cholesterol-lowering effect. Until recently, they were believed to have little or no impact on blood triglycerides (TG). However, studies taken individually were possibly lacking statistical power to detect modest TG decreases. This study was performed to quantify the TG-lowering effect of PS by pooling individual subject data from 12 randomised controlled trials that investigated the effects of PS on blood lipids.The main outcome variable was the control-adjusted PS effect on relative (%) and absolute (mmol/L) changes in TG. The relative and absolute changes in high-density lipoprotein cholesterol (HDL-C) were also assessed. Differences in changes of serum lipid concentrations between PS and control treatments were estimated by an ANCOVA using a random effect model which included PS intake (active or control), study and predefined subject characteristics.The twelve randomised controlled trials included in total 935 hypercholesterolaemic subjects not preselected based on their baseline TG concentrations. In most studies, the PS dose ranged between 1.6 and 2.5 g/day. PS intake significantly lowered serum TG by 6.0% (95% CI: −10.7, −1.2) or 0.12 mmol/L (95% CI: −0.20, −0.04). No significant interaction was observed between PS intake and baseline TG concentrations on relative changes, but, on absolute changes, interaction was significant with larger TG decreases observed with higher TG concentrations at baseline. No effects were observed on HDL-C concentrations.These results show that PS exert a modest TG-lowering effect which is dependent on baseline concentrations.
Keywords: Plant sterols; Triglycerides; Cholesterol; Pooled analysis; Diet and lifestyle

The objective of this study was to investigate the influence of high dietary iodine supply and different iodine sources on thyroid status and oxidative stress in target tissues of the thyroid hormones in fattening pigs.Eighty castrates (body weight: 33.3 ± 0.4 kg) were randomly allotted into five different treatments: The control diet contained 150 μg I/kg as KI, the other feeding groups were supplemented with 4,000 μg I/kg (as KI and KIO3) and 10,000 μg I/kg (as KI and KIO3), respectively. The mRNA expression levels of sodium/iodide symporter (NIS) and key antioxidant enzymes (Cu/Zn SOD, CAT, GPx) were analyzed in thyroid gland, liver, kidney, muscle, and adipose tissue sampled during slaughter. Furthermore, antioxidant enzyme activities and the effect on lipid peroxidation (MDA) were determined in liver and muscle.In thyroid gland, a significant downregulation of NIS and Cu/Zn SOD mRNA expression was observed in high-iodine groups. In liver, a source effect on the mRNA expression of Cu/Zn SOD between KI and KIO3 at 4,000 μg I/kg was shown. In contrast, not SOD but GPx activity was affected by iodine source with strongest downregulation in high KIO3 group. In muscle, GPx activity was affected by both iodine source and dose, showing stronger downregulation in KI groups. In kidney and adipose tissue, oxidative stress parameters showed no or only unsystematic changes. However, variation in iodine supply had no effect on MDA concentrations.NIS expression was significantly decreased with increased iodine supplementation, which is to ensure the thyroid gland function. However, the alleviating effect of iodine supplementation observed in antioxidant enzyme mRNA expression and activity did not reflect on the lipid peroxide level.
Keywords: Iodide; Iodate; NIS; Oxidative stress; Fattening pig

Serum taurine and risk of coronary heart disease: a prospective, nested case–control study by Oktawia P. Wójcik; Karen L. Koenig; Anne Zeleniuch-Jacquotte; Camille Pearte; Max Costa; Yu Chen (169-178).
Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk.We conducted a case–control study nested in the New York University Women’s Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels.Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber and iron, and negatively related to dietary intake of saturated fat (all p values ≤0.05). There was no statistically significant association between serum taurine levels and the risk of CHD in the overall study population. The adjusted ORs for CHD in increasing taurine tertiles were 1.0 (reference), 0.85 (95% CI, 0.51–1.40) and 0.66 (0.39–1.13; p for trend = 0.14). There was a significant inverse association between serum taurine and CHD risk among women with high total serum cholesterol (>250 mg/dL) (adjusted OR = 0.39 (0.19–0.83) for the third versus first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk.The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels.
Keywords: Taurine; Serum; Coronary heart disease; NYUWHS; Epidemiology

Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model by Jia Xiao; Yick Pang Ching; Emily C. Liong; Amin A. Nanji; Man Lung Fung; George L. Tipoe (179-191).
To investigate the hepato-protective properties and underlying mechanisms of SAMC in a non-alcoholic fatty liver disease (NAFLD) rat model.Female rats were fed with a diet comprising highly unsaturated fat diet (30% fish oil) for 8 weeks to develop NAFLD with or without an intraperitoneal injection of 200 mg/kg SAMC three times per week. After euthanasia, blood and liver samples of rats were collected for histological and biochemical analyses.Co-treatment of SAMC attenuated NAFLD-induced liver injury, fat accumulation, collagen formation and free fatty acids (FFAs). At the molecular level, SAMC decreased the lipogenesis marker and restored the lipolysis marker. SAMC also reduced the expression levels of pro-fibrogenic factors and diminished liver oxidative stress partly through the inhibition in the activity of cytochrome P450 2E1-dependent pathway. NAFLD-induced inflammation was also partially mitigated by SAMC treatment via reduction in the pro-inflammatory mediators, chemokines and suppressor of cytokine signaling. The protective effect of SAMC is also shown partly through the restoration of altered phosphorylation status of FFAs-dependent MAP kinase pathways and diminished in the nuclear transcription factors (NF-κB and AP-1) activity during NAFLD development.SAMC is a novel hepato-protective agent against NAFLD caused by abnormal liver functions. Garlic or garlic derivatives could be considered as a potent food supplement in the prevention of fatty liver disease.
Keywords: S-allylmercaptocysteine; NAFLD; Fibrosis; Oxidative stress; Inflammation

Research has demonstrated significant underreporting of food intake in obese individuals with and without binge eating disorder (BED). An improved understanding of the accuracy of self-reported food intake is central to diagnosis of eating disorders and monitoring response to treatment. The purpose was to: (1) confirm those with BED consume significantly more kilocalories (kcal) than overweight/obese controls when instructed to overeat in the laboratory and (2) compare dietary recall data with measured intake.Fifteen women fulfilling BED criteria and 17 controls participated in an overeating episode and completed a 24-h dietary recall.BED participants consumed significantly more kilocalories according to both methodologies. The BED group self-reported 90% of the measured intake compared to 98% for the control group. Mean differences between the methods indicated that on average both groups underreported intake; however, the mean difference between methods was significantly greater in the BED group.Findings confirm that those with BED consume significantly more than controls during a laboratory binge and controls tended to be more accurate in recalling their intake 24 h later.
Keywords: Binge eating disorder; Obesity; Food intake; Meal patterning; Dietary recall; Underreporting

Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density (BMD) in early postmenopausal women.In this 6-month double-blind pilot study, 70 subjects were randomized to receive daily either calcium only or the geniVida™ bone blend (GBB), which consisted of genistein (30 mg/days), vitamin D3 (800 IU/days), vitamin K1 (150 μg/days) and polyunsaturated fatty acids (1 g polyunsaturated fatty acids as ethyl ester: eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1). Markers of bone resorption and formation and BMD at the femoral neck, lumbar spine, Ward’s triangle, trochanter and intertrochanter, total hip and whole body were assessed.Subjects supplemented with the GBB (n = 30) maintained femoral neck BMD, whereas in the placebo group (n = 28), BMD significantly decreased (p = 0.007). There was also a significant difference (p < 0.05) in BMD between the groups at Ward’s triangle in favor of the GBB group. Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group. The GBB was well tolerated, and there were no significant differences in adverse events between groups.The GBB may help to prevent osteoporosis and reduce fracture risk, at least at the hip, in postmenopausal women. Larger and longer-term clinical trials are warranted.
Keywords: Genistein; Osteoporosis; Clinical trial; Isoflavones; Bone mineral density; Safety

Dietary fiber intake and risk of breast cancer by menopausal and estrogen receptor status by Qian Li; Theodore R. Holford; Yawei Zhang; Peter Boyle; Susan T. Mayne; Min Dai; Tongzhang Zheng (217-223).
Evaluate the hypothesis that relation of breast cancer associated with dietary fiber intakes varies by type of fiber, menopausal, and the tumor’s hormone receptor status.A case–control study of female breast cancer was conducted in Connecticut. A total of 557 incident breast cancer cases and 536 age frequency-matched controls were included in the analysis. Information on dietary intakes was collected through in-person interviews with a semi-quantitative food frequency questionnaire and was converted into nutrient intakes. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression.Among pre-menopausal women, higher intake of soluble fiber (highest versus lowest quartile of intake) was associated with a significantly reduced risk of breast cancer (OR = 0.38, 95% CI, 0.15–0.97, P trend = 0.08). When further restricted to pre-menopausal women with ER tumors, the adjusted OR for the highest quartile of intake was 0.15 (95% CI, 0.03–0.69, P trend = 0.02) for soluble fiber intake. Among post-menopausal women, no reduced risk of breast cancer was observed for either soluble or insoluble fiber intakes or among ER+ or ER tumor groups.The results from this study show that dietary soluble fiber intake is associated with a significantly reduced risk of ER breast cancer among pre-menopausal women. Additional studies with larger sample size are needed to confirm these results.
Keywords: Dietary fiber intake; Breast cancer; Estrogen receptor; Menopausal status; Case–control studies

Neuroprotective effects of digested polyphenols from wild blackberry species by Lucélia Tavares; Inês Figueira; Gordon J. McDougall; Helena L. A. Vieira; Derek Stewart; Paula M. Alves; Ricardo B. Ferreira; Cláudia N. Santos (225-236).
Blackberry ingestion has been demonstrated to attenuate brain degenerative processes with the benefits ascribed to the (poly)phenolic components. The aim of this work was to evaluate the neuroprotective potential of two wild blackberry species in a neurodegeneration cell model and compare them with a commercial variety.This work encompasses chemical characterization before and after an in vitro digestion and the assessment of neuroprotection by digested metabolites. Some studies targeting redox/cell death systems were also performed to assess possible neuroprotective molecular mechanisms.The three blackberry extracts presented some quantitative differences in polyphenol composition that could be responsible for the different responses in the neurodegeneration cell model. Commercial blackberry extracts were ineffective but both wild blackberries, Rubus brigantinus and Rubus vagabundus, presented neuroprotective effects. It was verified that a diminishment of intracellular ROS levels, modulation of glutathione levels and activation of caspases occurred during treatment. The last effect suggests a preconditioning effect since caspase activation was not accompanied by diminution in cell death and loss of functionality.This is the first time that metabolites obtained from an in vitro digested food matrix, and tested at levels approaching the concentrations found in human plasma, have been described as inducing an adaptative response.
Keywords: Caspase activity; Glutathione balance; In vitro digestion; Neurodegenerative diseases; Wild blackberries

This study proposes to examine the accuracy of four anthropometric indexes of obesity to identify the presence of hypertension and assess differences in the estimation and strength of effect measures of the association between each anthropometric measure and hypertension in Brazilian adults.A population-based cross-sectional study was carried out with a sample of 1,720 adults from Florianópolis, Brazil. Receiver operating characteristic (ROC) curves were performed to identify the sensitivity and specificity of the best cutoff values for anthropometric indexes (body mass index—BMI, waist circumference—WC, waist-to height ratio—WHtR and conicity index—C-index) for prediction of hypertension. The associations between anthropometric indexes and hypertension were analyzed by Poisson regression expressed as Prevalence Ratios (95% CI) adjusted for socio-demographic variables, health behavior, height, and anthropometric indexes.Of the four anthropometric indexes studied, BMI, WC, and WHtR were found to have the largest areas under the ROC curve relative to hypertension in both sexes. The cutoff values in women and men associated with presence of hypertension were BMI of 24.9 and 24.6 kg/m², WC of 86.2 and 89.5 cm, WHtR of 0.49 and 0.50, and C-index of 1.15 and 1.18, respectively. WC and BMI had greater magnitude of association with presence of hypertension, adjusting for socio-demographic variables, health behavior, height, and anthropometric indexes in women and men, respectively.Anthropometric indexes provide an effective, simple, inexpensive, and non-invasive means for a first-level screening for hypertension.
Keywords: Anthropometric indexes; Blood pressure; Central obesity; Diagnosis; Hypertension; Sensitivity

A composite score combining waist circumference and body mass index more accurately predicts body fat percentage in 6- to 13-year-old children by I. Aeberli; M. Gut-Knabenhans; R. S. Kusche-Ammann; L. Molinari; M. B. Zimmermann (247-253).
Body mass index (BMI) and waist circumference (WC) are widely used to predict % body fat (BF) and classify degrees of pediatric adiposity. However, both measures have limitations. The aim of this study was to evaluate whether a combination of WC and BMI would more accurately predict %BF than either alone.In a nationally representative sample of 2,303 6- to 13-year-old Swiss children, weight, height, and WC were measured, and %BF was determined from multiple skinfold thicknesses. Regression and receiver operating characteristic (ROC) curves were used to evaluate the combination of WC and BMI in predicting %BF against WC or BMI alone. An optimized composite score (CS) was generated.A quadratic polynomial combination of WC and BMI led to a better prediction of %BF (r 2 = 0.68) compared with the two measures alone (r 2 = 0.58–0.62). The areas under the ROC curve for the CS [0.6 * WC-SDS + 0.4 * BMI-SDS] ranged from 0.962 ± 0.0053 (overweight girls) to 0.982 ± 0.0046 (obese boys) and were somewhat greater than the AUCs for either BMI or WC alone. At a given specificity, the sensitivity of the prediction of overweight and obesity based on the CS was higher than that based on either WC or BMI alone, although the improvement was small.Both BMI and WC are good predictors of %BF in primary school children. However, a composite score incorporating both measures increased sensitivity at a constant specificity as compared to the individual measures. It may therefore be a useful tool for clinical and epidemiological studies of pediatric adiposity.
Keywords: Waist circumference; Body fat; Body mass index; Overweight; Children

Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined.Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21–81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39).For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078).Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status.
Keywords: Copper; Selenium; Zinc; Trace element; Haemochromatosis; Iron overload

Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols by Annalisa Aggio; Davide Grassi; Eugenia Onori; Antonio D’Alessandro; Francesco Masedu; Marco Valenti; Claudio Ferri (263-272).
At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure–activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.The effects of two catechins, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.At resting tension, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01–10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.
Keywords: Flavanols; Flavonoids; Endothelium; Nitric oxide; Vasorelaxation

Suboptimal maternal vitamin D status and low education level as determinants of small-for-gestational-age birth weight by Gerrit van den Berg; Manon van Eijsden; Tanja G. M. Vrijkotte; Reinoud J. B. J. Gemke (273-279).
This study aimed firstly to investigate the contribution of maternal 25(OH) vitamin D to the association of maternal education and small-for-gestational-age birth weight (SGA) and secondly to examine whether the contribution of 25(OH) vitamin D differs by overweight, season, and maternal smoking.Logistic regression analysis was carried out in this study, using data of 2,274 pregnant women of Dutch ethnicity from the ABCD study, a population-based cohort study in the Netherlands. Maternal 25(OH) vitamin D was measured in early pregnancy. Stratified analyses were conducted for overweight, season of blood sampling, and smoking.Low-educated women had lower 25(OH) vitamin D levels compared to high-educated women, and women in the lowest 25(OH) vitamin D quartile had a higher risk of SGA offspring. In addition, low-educated women had a higher risk of SGA offspring (OR 1.95 [95% CI: 1.20–3.14]). This association decreased with 7% after adjustment for 25(OH) vitamin D (OR 1.88 [95% CI 1.16–3.04]). In stratified analyses, adjustment for 25(OH) vitamin D resulted in a decrease in OR of about 17% in overweight women and about 15% in women who conceived in wintertime.25(OH) vitamin D appears to be a modifiable contributor to the association between low maternal education and SGA offspring, particularly in overweight women and women who conceived in the winter period. In those women, increasing the intake of vitamin D, either through dietary adaptation or through supplementation in order to achieve the recommendation, could be beneficial.
Keywords: 25(OH) vitamin D; Small-for-gestational-age; Maternal education; Overweight; Season; Smoking

Simultaneous ingestion of dietary proteins reduces the bioavailability of galloylated catechins from green tea in humans by Sarah Egert; Jane Tereszczuk; Silvia Wein; Manfred James Müller; Jan Frank; Gerald Rimbach; Siegfried Wolffram (281-288).
To investigate the influence of dietary proteins (casein, soy protein) and skimmed milk on the plasma kinetics of green tea (GT) catechins.In a randomized cross-over design with one-week intervals, 24 healthy normal-weight women consumed a test drink containing 1.75 g GT extract with or without the addition of different proteins. Treatments were GT (control), GT with skimmed milk (GT + M), GT with caseinate (GT + CS), or GT with soy protein (GT + S). Venous blood samples were taken before and several times during a period of 4.5 h after consumption of the test drink. Plasma concentrations of catechins were analyzed by HPLC with electrochemical detection.Compared to control, consumption of GT with milk, caseinate, or soy protein significantly reduced the bioavailability (mean area under the plasma concentration–time curve) of total catechins (means ± SEM; GT + M, 87 ± 5%; GT + CS, 79 ± 5%; GT + S, 88 ± 4%), epigallocatechin gallate (GT + M, 68 ± 4%; GT + CS, 63 ± 5%; GT + S, 76 ± 5%), and epicatechin gallate (GT + M, 68 ± 5%; GT + CS, 66 ± 6%; GT + S, 77 ± 6%), while the bioavailability of non-galloylated catechins such as epigallocatechin (GT + M, 134 ± 9%; GT + CS, 118 ± 9 %; GT + S, 123 ± 8%) and epicatechin (GT + M, 125 ± 10%; GT + CS, 114 ± 11%; GT + S, 110 ± 8%) significantly increased. No significant differences in bioavailability of GT catechins were observed between the treatments GT + M, GT + CS, or GT + S.Simultaneous ingestion of dietary proteins reduces the bioavailability of galloylated catechins from GT in humans.
Keywords: Catechins; Flavan-3-ols; Bioavailability; Dietary protein; Human study

Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells by Andreas J. Flammer; Elizabeth A. Martin; Mario Gössl; R. Jay Widmer; Ryan J. Lennon; Jasmine A. Sexton; Darrell Loeffler; Sundeep Khosla; Lilach O. Lerman; Amir Lerman (289-296).
Cranberry juice (CJ) contains a remarkably high concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 × 230 ml) over 4 months has beneficial effects on vascular function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular.A total of 84 participants (49.5 ± 16.2 years) with peripheral endothelial dysfunction and cardiovascular risk factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol—32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry.Baseline characteristics were similar in both groups. The effect of CJ on peripheral endothelial function and on circulating EPC counts (CD34+/CD133+/KDR+) did not change during the study. A high percentage of EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared to placebo, induced a decrease in the fraction of EPCs expressing osteocalcin (−8.64 ± 48.98 and 19.13 ± 46.11%, respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated significantly with the number of EPCs expressing osteocalcin.The study demonstrated that long-term supplementation of polyphenol-rich CJ did not improve peripheral endothelial function. However, the decrease in the fraction of osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ.
Keywords: Endothelial function; Cranberry; Polyphenols; Endothelial progenitor cells; Osteocalcin

Effect of dietary calcium (Ca) on body composition and Ca metabolism during growth in genetically obese (β) male rats by Clarisa Marotte; Adriana Weisstaub; Gabriel Bryk; Maria C. Olguin; Marta Posadas; Diego Lucero; Laura Schreier; Maria Luz Pita Martín de Portela; Susana N. Zeni (297-305).
Obese β rats may be a suitable model to evaluate the association between calcium intake (CaI) and obesity during growth.The present study comparatively evaluated Ca absorption and retention, and changes in body composition in spontaneously genetically obese (β) male rats fed three different dietary Ca levels: high 0.9% (HCa); normal: 0.5% (NCa); low: 0.2% (LCa).Pregnant rats were fed isocaloric diets which varied in Ca content only. Male pups continued feeding the same maternal diet until postnatal day 60. The percentage of Apparent Ca absorption (CaA %), Ca balance (CaB), body composition, glucose, triglycerides (TGL), and insulin levels were evaluated.Food consumption and body weight (BW) were higher in Group LCa than in Groups NCa and HCa (p < 0.01); no differences were observed between the latter two groups. Group LCa presented the highest body fat, liver weight, perigonadal and retroperitoneal fat (p < 0.05); conversely, body ashes and total skeleton bone mineral content were significantly lower compared with animals in both the NCa (p < 0.01) and HCa groups (p < 0.01). CaB (mg/day) reached a plateau at the highest CaI (mg/day) value (r = 0.985, p < 0.001). CaA%, serum glucose, insulin, and TGL levels rose as CaI decreased (p < 0.01).Although further studies are required, low Ca consumption in this strain of rats could modulate BW inducing changes in several lipid metabolism parameters, which in turn lead to an increase in body fat.
Keywords: Low calcium diet; Bone mass; Fat

Metabolic syndrome and quality of life in the elderly: age and gender differences by Alice Laudisio; Emanuele Marzetti; Livia Antonica; Francesco Pagano; Davide L. Vetrano; Roberto Bernabei; Giuseppe Zuccalà (307-316).
The metabolic syndrome (MetS) is highly prevalent in Western older populations. MetS is an intriguing entity, because it includes potentially reversible risk factors. Some studies have suggested an inverse correlation between MetS and health-related quality of life (HRQoL), but data regarding older subjects are scanty and conflicting. The aim of this study was to assess the association between HRQoL and MetS in older, unselected community-dwelling subjects.We analyzed data of 356 subjects aged 75+ living in Tuscania (Italy). HRQoL was assessed using the Health Utilities Index, Mark 3. Diagnosis of MetS was defined according to the National Cholesterol Education Program’s ATP-III criteria.MetS was reported by 137 (38%) participants. According to linear regression analysis, MetS was associated with significantly better HRQoL in men (B = 0.19 95% CI = 0.06–0.32; p = 0.006), but not in women. Also, when the regression model was analyzed in men, MetS was associated with better HRQoL (B = 0.17, 95% CI = 0.01–0.32; p = 0.035) only among participants aged 80+. No significant associations were found in men between HRQoL and any of the single components of MetS.MetS is not associated with worse HRQoL among community-dwelling elderly; it is associated with significantly better HRQoL among the oldest men.
Keywords: Metabolic syndrome; Quality of life; Elderly; Epidemiology

To compare the effects of two low-fat, hypoenergetic diets differing in carbohydrate-to-protein ratio, on strength and aerobic capacity measures in overweight and obese men.In a parallel design, 56 men (age, 45.5 ± 8.7 years; BMI, 33.6 ± 3.9 kg/m2) were randomly assigned to a low-fat, energy-restricted diet (7,000 kJ/day) with either high protein (HP: protein/carbohydrate/fat % energy, 35:40:25) or standard protein (SP, 17:58:25). Body weight, body composition, muscle strength and aerobic capacity were assessed at baseline and after 12 weeks.Forty-two participants completed the study (HP, n = 21; SP, n = 21). Both groups experienced similar reductions in body weight (HP, −10.7 ± 5.3 kg [−9.8%]; SP, −8.7 ± 3.5 kg [−8.4%]) and fat-free mass (HP, −2.8 ± 3.6 kg; SP, −3.2 ± 2.7 kg; P < 0.001 time; P > 0.14 time × group interaction). There was a trend for a greater reduction in fat mass in the HP diet group, (−7.7 ± 4.3 kg [−21.2%] vs. −5.4 ± 3.3 kg [−15.1%]; P < 0.001 time; P = 0.06 time × group interaction). Absolute peak oxygen uptake did not change in either group (P = 0.39 time; P = 0.50 time × group interaction). Overall, in both groups, relative peak oxygen uptake increased (2.9 ± 2.8 ml kg−1 min−1 [8.9%]), peak isometric knee extensor strength increased (14.1 ± 35.7 Nm [7.1%]) and peak handgrip strength decreased (−1.6 ± 4.1 kg [−3%]) (P ≤ 0.02 time for all), with no diet effect (P ≤ 0.23 time × group interaction).In overweight and obese men, both a HP and SP diet reduced body weight and improved body composition with similar effects on strength and aerobic capacity.
Keywords: Diet composition; Exercise capacity; Weight loss; Physical function; Nutrition

The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother–child cohort study in Crete, Greece (Rhea study) by Eleni Papadopoulou; Nikolaos Stratakis; Theano Roumeliotaki; Katerina Sarri; Domenic F. Merlo; Manolis Kogevinas; Leda Chatzi (327-336).
We examined whether high doses of folic acid and iron supplementation in early-to-mid pregnancy affect the risk of preterm birth, low birth weight, and small for gestational age neonates, in the mother–child cohort in Crete, Greece (Rhea study).We included 1,279 women with singleton pregnancies with complete data on supplements use in early-to-mid pregnancy and birth outcomes. Anthropometric measurements at birth were obtained from medical records. Red blood cell folate concentrations in cord blood were measured in a subsample of the study population (n = 58).Sixty-six percent of the study participants reported high doses of supplemental folic acid use (5 mg/day), while 21 % reported excessive doses of folic acid use (>5 mg/day) in early-to-mid pregnancy. Daily intake of 5-mg supplemental folic acid was associated with a 31 % decrease in the risk of preterm birth (RR, 0.69; 95 % CI, 0.44, 0.99), 60 % decrease in the risk of delivering a low birth weight neonate (RR, 0.40; 95 % CI, 0.21, 0.76), and 66 % decrease in the risk of delivering a small for gestational age (SGA) neonate (RR, 0.34; 95 % CI, 0.16, 0.73). Daily doses of iron supplementation more than 100 mg were associated with a twofold increased risk for SGA neonates (RR, 2.14; 95 % CI, 0.99, 5.97).These findings suggest that high daily doses of supplementary folic acid in early-to-mid pregnancy may be protective for preterm birth, low birth weight, and small for gestational age neonates, while high daily doses of supplementary iron may be harmful for fetal growth.
Keywords: Folic acid; Iron; Supplements; Pregnancy; Preterm birth; Fetal growth

Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress by Jukka Montonen; Heiner Boeing; Andreas Fritsche; Erwin Schleicher; Hans-Georg Joost; Matthias B. Schulze; Annika Steffen; Tobias Pischon (337-345).
To examine the association of red meat and whole-grain bread consumption with plasma levels of biomarkers related to glucose metabolism, oxidative stress, inflammation and obesity.Our cross-sectional study was based on 2,198 men and women who were selected as a sub-cohort for an investigation of biological predictors of diabetes and cardiovascular diseases from the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Circulating levels of glycated hemoglobin, adiponectin, hs-CRP, gamma-glutamyltransferase, alanine-aminotransferase, fetuin-A, HDL-cholesterol and triglycerides were measured from random blood samples. Diet and lifestyle data were assessed by questionnaires, and anthropometric data were measured.After multivariable adjustment, higher consumption of whole-grain bread was significantly (P trend <0.05) associated with lower levels of GGT, ALT and hs-CRP, whereas higher consumption of red meat was significantly associated with higher levels of GGT and hs-CRP when adjusted for potential confounding factors related to lifestyle and diet. Further adjustment for body mass index and waist circumference attenuated the association between red meat and hs-CRP (P = 0.19).The results of this study suggest that high consumption of whole-grain bread is related to lower levels of GGT, ALT and hs-CRP, whereas high consumption of red meat is associated with higher circulating levels of GGT and hs-CRP.
Keywords: Red meat; Whole grain; Biomarkers; Glucose metabolism

We explored the pathophysiologic mechanisms of long-term fructose-induced lower urinary tract symptoms (LUTS) in rats.Male Wistar rats were fed with fructose for 3 or 6 months. Biochemical and transcystometric parameters were compared between fructose-fed and age-matched normal-diet rats. Pelvic nerve and external urethral sphincter-electromyogram activity recordings were performed to investigate fructose effects on neural control of bladders. Mitochondrial structure, ATP and acetylcholine content and purinergic and muscarinic cholinergic receptors were examined. Cytosolic cytochrome C staining by Western blot and immunocytochemistry for mitochondrial injury and PGP 9.5 stain for nerve density were also determined.The fructose-fed rats with higher plasma triglyceride, LDL and fasting glucose levels displayed LUTS with increased frequency and suppressed voiding contractile amplitude in phase 1 and phase 2 duration versus normal-diet control. Fructose feeding altered the firing types in pelvic afferent and efferent nerves and external urethral sphincter-electromyogram activity. Increased mast cell number, disrupted and swollen mitochondria, increased cytosolic cytochrome C stain and expression and decreased nerve density in bladder smooth muscle layers appeared in the fructose-fed rats. Fructose feeding also significantly reduced ATP and acetylcholine content and enhanced protein expression of postsynaptic P2X1, P2X2 and P2X3 purinergic receptors and M2 and M3 muscarinic cholinergic receptors expression in the smooth muscles of urinary bladder.Long-term fructose feeding induced neuropathy and myopathy in the urinary bladders. Impaired mitochondrial integrity, reduced nerve density, ATP and acetylcholine content and upregulation of purinergic and muscarinic cholinergic receptors expression may contribute to the bladder dysfunction of fructose-fed animals.
Keywords: Urinary bladder; Metabolic syndrome; Male rats; Purinergic receptor; Muscarinic receptor

Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease: the FLAVURS trial by Mary F. Chong; Trevor W. George; Dauren Alimbetov; Yannan Jin; Michelle Weech; Anna L. Macready; Jeremy P. E. Spencer; Orla B. Kennedy; Anne-Marie Minihane; Michael H. Gordon; Julie A. Lovegrove (361-378).
Limited robust randomised controlled trials investigating fruit and vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist. We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F&V consumption on nutrient biomarker profile.A parallel, randomised, controlled, dose–response dietary intervention study. Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week periods during the 18-week study.Compliance to target numbers and types of F&V was broadly met and verified by dietary records, and plasma and urinary biomarkers. Mean (±SEM) number of F&V portions/day consumed by the HF and LF groups at baseline (3.8 ± 0.3 and 3.4 ± 0.3), 6 weeks (6.3 ± 0.4 and 5.8 ± 0.3), 12 weeks (7.0 ± 0.3 and 6.8 ± 0.3) and 18 weeks (7.6 ± 0.4 and 8.1 ± 0.4), respectively, was similar at baseline yet higher than the CT group (3.9 ± 0.3, 4.3 ± 0.3, 4.6 ± 0.4, 4.5 ± 0.3) (P = 0.015). There was a dose-dependent increase in dietary and urinary flavonoids in the HF group, with no change in other groups (P = 0.0001). Significantly higher dietary intakes of folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P = 0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups compared with CT, which were broadly supported by nutrient biomarker analysis.The success of improving nutrient profile by active encouragement of F&V intake in an intervention study implies the need for a more hands-on public health approach.
Keywords: Fruits and vegetables; Flavonoids; Biomarkers; Dose response

Capsaicinoids lower plasma cholesterol and improve endothelial function in hamsters by Yin Tong Liang; Xiao-Yu Tian; Jing Nan Chen; Cheng Peng; Ka Ying Ma; Yuanyuan Zuo; Rui Jiao; Ye Lu; Yu Huang; Zhen-Yu Chen (379-388).
Capsaicinoids are the active compounds in chili pepper. The present study investigated the effect of capsaicinoids on plasma lipids, functionality of aorta including atherosclerotic plaque development, cholesterol absorption biomarker, fecal sterol excretion, and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism.Hamsters were divided into five groups and fed a high-cholesterol diet containing 0 % (CON), 0.010 % (LD), 0.015 % (MD), 0.020 % (HD), and 0.030 % (VD) capsaicinoids, respectively, for 6 weeks. Plasma lipids were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. Endothelial function was assessed by measuring the acetylcholine-induced endothelium-dependent relaxations in aorta.Capsaicinoids reduced plasma total cholesterol, non-high-density lipoprotein cholesterol, and triacylglycerols with high-density lipoprotein cholesterol being unaffected. All four experimental groups had a decrease in the atherosclerotic plaque compared with CON. Dietary capsaicinoids increased the fecal excretion of total acidic sterols possibly mediated by up-regulation of cholesterol 7α-hydroxylase and down-regulation of liver X receptor alpha. Plasma sterol analysis demonstrated that capsaicinoids decreased the ratio of plasma campesterol/cholesterol, suggesting they decreased cholesterol absorption. Capsaicinoids could improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2. However, no dose-dependent effect of capsaicinoids on these parameters was seen.Capsaicinoids were beneficial in improving lipoprotein profile and aortic function in hamsters fed a high-cholesterol diet.
Keywords: Cholesterol; Capsaicin; Capsaicinoids; Aorta; CYP7A1; COX-2; Vascular reactivity

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake by Gunter G. C. Kuhnle; Annemiek M. C. P. Joosen; Catherine J. Kneale; Tamsin C. O’Connell (389-395).
Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies.In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake.The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed.There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples.The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake.
Keywords: Stable isotope ratio; Dietary assessment; Nutritional biomarker; Fish; Meat

Red wine contains many potentially bioactive polyphenols including resveratrol, catechins, anthocyanins and flavonoids as well as tannins derived from oak during maturation. This study examined the effects of a mixture of ellagitannins from oak bark (Quercus petraea L.) on cardiovascular, metabolic and liver changes in high-carbohydrate, high-fat diet–fed rats and in Spontaneously Hypertensive Rats (SHR).First, 8-week-old male Wistar rats were divided into four groups and given either cornstarch diet, cornstarch diet + oak bark extract (0.5 mL/kg food), high-carbohydrate, high-fat diet or high-carbohydrate, high-fat diet + oak bark extract (0.5 mL/kg food) for 16 weeks. Oak bark extract was added to the diets for last 8 weeks of the feeding period. Secondly, SHR aged 42 weeks fed on standard chow diet were divided into two groups with and without oak bark extract treatment for 12 weeks (0.5 mL/kg food).The high-carbohydrate, high-fat diet induced signs of metabolic syndrome along with cardiovascular remodelling and non-alcoholic steatohepatitis. Oak bark extract attenuated the signs of metabolic syndrome in high-carbohydrate, high-fat diet–fed rats and improved the structure and function of the heart and the liver. SHR after oak bark extract treatment for 12 weeks showed lower systolic blood pressure, lower cardiac fibrosis and cardiac stiffness and improved vascular reactivity.Oak bark extract containing ellagitannins improved cardiovascular, metabolic and liver parameters in these rat models of human disease, suggesting that part of the benefits attributed to red wine may be produced by these ellagitannins.
Keywords: Obesity; Cardiovascular disease; Dyslipidaemia; Ellagitannins; Hypertension

Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB pathway by Ji-Young Lee; Min-Sup Lee; Hee-Jeon Choi; Ji-Woong Choi; Taisun Shin; Hee-Chul Woo; Jae-Il Kim; Hyeung-Rak Kim (409-421).
Laminaria japonica is a representative marine brown alga used as a culinary item in East Asia. L. japonica extract was shown to exert various biological activities; however, its anti-inflammatory activity has not been reported. The aim of this study is to investigate the molecular mechanisms underlying its anti-inflammatory action.Anti-inflammatory mechanisms of L. japonica n-hexane fraction (LHF) were assessed using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. An anti-inflammatory compound isolated from LHF by reverse-phase chromatography was identified using nuclear magnetic resonance (NMR) spectroscopy.Our results indicate that LHF significantly inhibited LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) secretion in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) with no cytotoxicity. As results, levels of pro-inflammatory cytokines were significantly reduced by pretreatment of LHF in LPS-stimulated RAW 264.7 cells. Treatment of LHF strongly suppressed nuclear factor-κB (NF-κB) promoter-driven expression and nuclear translocation of NF-κB by preventing proteolytic degradation of inhibitor of κB (IκB)-α in LPS-stimulated RAW 264.7 cells. Moreover, LHF inhibited the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. One of the anti-inflammatory compounds was isolated from LHF and identified as fucoxanthin.These results indicate that the LHF-mediated inhibition of NO and PGE2 secretion in LPS-stimulated macrophages is regulated by NF-κB inactivation through inhibition of IκB-α, MAPKs, and Akt phosphorylation. LHF may be considered as a functional food candidate for the prevention or treatment of inflammatory diseases.
Keywords: Anti-inflammation; Fucoxanthin; Laminaria japonica ; MAP kinases; NF-kappaB; RAW 264.7 cells

Erratum to: Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake by Gunter G. C. Kuhnle; Annemiek M. C. P. Joosen; Catherine J. Kneale; Tamsin C. O’Connell (423-423).

Erratum to: Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB pathway by Ji-Young Lee; Min-Sup Lee; Hee-Jeon Choi; Ji-Woong Choi; Taisun Shin; Hee-Chul Woo; Jae-Il Kim; Hyeung-Rak Kim (427-427).