European Journal of Nutrition (v.56, #3)

Dietary guidance for lutein: consideration for intake recommendations is scientifically supported by Katherine M. Ranard; Sookyoung Jeon; Emily S. Mohn; James C. Griffiths; Elizabeth J. Johnson; John W. Erdman Jr. (37-42).
Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine’s recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases. Lupton et al. developed a set of nine criteria to determine whether a bioactive is ready to be considered for DRI-like recommendations. These criteria include: (1) an accepted definition; (2) a reliable analysis method; (3) a food database with known amounts of the bioactive; (4) cohort studies; (5) clinical trials on metabolic processes; (6) clinical trials for dose–response and efficacy; (7) safety data; (8) systematic reviews and/or meta-analyses; (9) a plausible biological rationale. Based on a review of the literature supporting these criteria, lutein is ready to be considered for intake recommendations. Establishing dietary guidance for lutein would encourage the consumption of lutein-containing foods and raise public awareness about its potential health benefits.
Keywords: Lutein; Intake recommendations; Bioactives; Visual performance; Macular degeneration

Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials by Sabine Baumgartner; Rouyanne T. Ras; Elke A. Trautwein; Ronald P. Mensink; Jogchum Plat (909-923).
Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations.Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-cryptoxanthin) using a random effects model. Heterogeneity was assessed using predefined subject and treatment characteristics.Average plant sterol or stanol intake was 2.5 g/d. Relative non-standardized and TC-standardized concentrations of β-carotene decreased by, respectively, −16.3 % (95 % CI −18.3; −14.3) and −10.1 % (−12.3; −8.0), α-carotene by −14.4 % (−17.5; 11.3) and −7.8 % (−11.3; −4.3), and lycopene by −12.3 % (−14.6; −10.1) and −6.3 % (−8.6; −4.0). Lutein concentrations decreased by −7.4 % (−10.1; −4.8), while TC-standardized concentrations were not changed. For zeaxanthin, these values were −12.9 % (−18.9; −6.8) and −7.7 % (−13.8; −1.7) and for β-cryptoxanthin −10.6 % (−14.3; −6.9) and −4.8 % (−8.7; −0.9). Non-standardized α-tocopherol concentrations decreased by −7.1 % (−8.0; −6.2) and γ-tocopherol by −6.9 % (−9.8; −3.9), while TC-standardized tocopherol concentrations were not changed. Non-standardized retinol and vitamin D concentrations were not affected. Results were not affected by baseline concentrations, dose, duration and type of plant sterols/stanols, except for significant effects of duration (≤4 vs. >4 weeks) on TC-standardized lutein concentrations (1.0 vs. −5.6 %) and type of plant sterol/stanol on TC-standardized β-carotene concentrations (−8.9 vs. −14.2 %).Plant sterol and stanol intake lowers TC-standardized hydrocarbon carotenoid concentrations, differently affects TC-standardized oxygenated carotenoid concentrations, but does not affect TC-standardized tocopherol concentrations or absolute retinol and vitamin D concentrations. Observed concentrations remained within normal ranges.
Keywords: Plant sterols; Plant stanols; Cholesterol; Hydrocarbon carotenoids; Oxygenated carotenoids; Fat-soluble vitamins

Metabolic syndrome and dietary patterns: a systematic review and meta-analysis of observational studies by Míriam Rodríguez-Monforte; Emília Sánchez; Francisco Barrio; Bernardo Costa; Gemma Flores-Mateo (925-947).
Lifestyle is linked to the risk of developing metabolic syndrome (MetS); however, its relationship with dietary patterns remains unclear. This systematic review and meta-analysis aims to analyse the association of a posteriori dietary patterns with the metabolic syndrome.The PubMed, CINAHL and Scopus databases were searched for epidemiological studies of dietary patterns and MetS. The association between dietary patterns and MetS was estimated using a random-effects meta-analysis with 95 % confidence intervals (CIs).A total of 28 cross-sectional studies and three cohort studies were included in the meta-analysis. In a comparison of the highest to the lowest category of prudent/healthy dietary patterns, the pooled odds ratio (OR) for MetS was 0.83 (95 % CI 0.76, 0.90; P for heterogeneity =0.0; and I 2 = 72.1 %) in cross-sectional studies, and the pooled relative risk (RR) for MetS in cohort studies was 0.91 (95 % CI 0.68, 1.21; P for heterogeneity =0.005; I 2 = 81.1 %). The pooled OR for MetS in a comparison of the highest to the lowest category of Western dietary patterns was 1.28 (95 % CI 1.17, 1.40; P for heterogeneity =0.0; and I 2 = 72.0 %) in cross-sectional studies, and the RR was 0.96 (95 % CI 0.53, 1.73; P for heterogeneity =0.102; I 2 = 62.6 %) in cohort studies.The results from cross-sectional studies showed that a prudent/healthy pattern is associated with a lower prevalence of MetS, whereas a Western/unhealthy is associated with an increased risk for MetS. Additional prospective studies are needed to confirm the association between dietary patterns and MetS.
Keywords: Dietary patterns; Metabolic syndrome; Systematic review; Meta-analysis

Inhibitory effects of Kaempferia parviflora extract on monocyte adhesion and cellular reactive oxygen species production in human umbilical vein endothelial cells by Satoru Horigome; Izumi Yoshida; Shihomi Ito; Shuichi Inohana; Kei Fushimi; Takeshi Nagai; Akihiro Yamaguchi; Kazuhiro Fujita; Toshiya Satoyama; Shin-ichi Katsuda; Shinobu Suzuki; Masatoshi Watai; Naoto Hirose; Takahiro Mitsue; Hitoshi Shirakawa; Michio Komai (949-964).
The rhizome of Kaempferia parviflora (KP) is used in traditional Thai medicine. In this study, we investigated the effects of an ethanol KP extract and two of its components [5,7-dimethoxyflavone (DMF) and 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (TMF)] on monocyte adhesion and cellular reactive oxygen species (ROS) production in human umbilical vein endothelial cells (HUVECs), which provide an in vitro model of events relevant to the development and progression of atherosclerosis.RAW264.7 mouse macrophage-like cells were incubated with various concentrations of KP extract or polymethoxyflavonoids and stimulated with lipopolysaccharide prior to measuring nitrite levels in the culture media. Monocyte adhesion was evaluated by measuring the fluorescently labeled human monocytic leukemia THP-1 cells that is attached to tumor necrosis factor-α (TNF-α)-stimulated HUVECs. Cellular ROS production was assessed by measuring cellular antioxidant activity using pyocyanin-stimulated HUVECs.KP extract and DMF reduced nitrite levels (as indicator of nitric oxide production) in LPS-stimulated RAW264.7 cells and also inhibited THP-1 cell adhesion to HUVECs. These treatments induced mRNA expression of endothelial nitric oxide synthase in TNF-α-stimulated HUVECs and downregulated that of various cell adhesion molecules, inflammatory mediators, and endothelial function-related genes. Angiotensin-converting enzyme activity was inhibited by KP extract in vitro. Furthermore, KP extract, DMF, and TMF inhibited the production of cellular ROS in pyocyanin-stimulated HUVECs.KP extract, DMF, and TMF showed potential anti-inflammatory and antioxidant effects in these in vitro models, properties that would inhibit the development and progression of atherosclerosis.
Keywords: Kaempferia parviflora ; HUVECs; Cell adhesion; Inflammatory mediator; Polymethoxyflavonoid; Atherosclerosis

Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area by Hye Jeong Kim; Na Kyung Kim; Hyeong Kyu Park; Dong Won Byun; Kyoil Suh; Myung Hi Yoo; Yong-Ki Min; Sun Wook Kim; Jae Hoon Chung (965-971).
The relationship between iodine intake and development of thyroid diseases shows a U-shaped curve with an increase of risk in both deficient and excessive iodine intakes. Our aim was to investigate the relationship between iodine intake and thyroid cancer in patients with thyroid nodules in an iodine-replete area.Retrospective analysis of 1170 patients with thyroid nodules was performed. Urinary iodine concentration (UIC) was measured by inductively-coupled plasma mass spectrometry. Predictive factors for thyroid cancer were evaluated using multivariate logistic regression models. The median UIC in all patients with thyroid nodules was 360 μg/L (range from 4 to 9631 μg/L). More than half of the patients (650/1170, 56 %) belonged to the category of excessive iodine intake (UIC ≥ 300 μg/L) according to WHO iodine recommendations. Patients with thyroid cancer were more likely to be distributed in UIC < 300 μg/L and in UIC ≥ 2500 μg/L than those with benign thyroid nodules. Male gender (OR 1.528, p = 0.028) and UIC were independent predictors for thyroid cancer. The multivariate-adjusted OR (95 % CI) in the relatively low (UIC < 300 μg/L) and extremely excessive (UIC ≥ 2500 μg/L) iodine intake groups for thyroid cancer were 1.519 (1.099–2.098) and 1.874 (1.094–3.208), respectively, compared to the other iodine intake group (300–2499 μg/L).Male gender and UIC were independent predictors of thyroid cancer in patients with thyroid nodules. This study suggests that relatively low and extremely excessive iodine intakes are associated with thyroid cancer in an iodine-replete area.
Keywords: Iodine; Thyroid nodules; Thyroid cancer

Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes by Kristyen A. Tomcik; William J. Smiles; Donny M. Camera; Helmut M. Hügel; John A. Hawley; Rani Watts (973-979).
Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro.Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 μg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined.Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P < 0.05), whereas all conditions increased SLC6A8 protein expression above CON at this time (P < 0.05). Changes in insulin signaling were demonstrated via increases in AktThr308 phosphorylation, with CR + INS > CON and CR at 1 h (P < 0.05) and with CR + INS + FEN > CON, CR, and CR + INS at 4 h (P < 0.05). In contrast, no changes in PKCζ/λ or GLUT4 phosphorylation were detected.Fenugreek, when combined with insulin, modulates creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.
Keywords: Creatine content; Creatine transport; Fenugreek supplement; Insulin signaling

Dietary intake of subjects with diabetes is inadequate in Switzerland: the CoLaus study by Pedro Marques-Vidal; Peter Vollenweider; Matthieu Grange; Idris Guessous; Gérard Waeber (981-989).
To characterize the dietary intake of subjects aged 40–80 years according to self-reported diabetes and presence of an anti-diabetic diet. Cross-sectional study conducted between 2009 and 2012 on 4289 participants (2274 women) living in Lausanne. Of the 299 (7 %) participants with self-reported diabetes, only 151 (51 %) reported an anti-diabetic diet. Compared to participants not reporting diabetes, participants with self-reported diabetes (with or without a diet) had a higher consumption of artificial sweeteners (0.3 ± 0.7 vs. 0.4 ± 0.8 and 0.8 ± 1.0 times/day) and a lower consumption of honey/jam (mean ± standard deviation: 0.5 ± 0.5 vs. 0.4 ± 0.4 and 0.4 ± 0.4 times/day) or sugar (0.6 ± 0.9 vs. 0.4 ± 0.7 and 0.2 ± 0.5 times/day) for participants not reporting diabetes, participants with self-reported diabetes not on a diet and on a diet, respectively. Compared to participants not on a diet, participants on a diet had a higher consumption of vegetables (1.8 ± 1.3 vs. 1.4 ± 1.0 portions/day), while no differences were found regarding all other food groups and nutrients. Participants with self-reported diabetes on a diet had a higher consumption of meat (5.6 ± 3.6 vs. 4.8 ± 2.9 portions/week) and a lower consumption of simple carbohydrates (21.0 ± 7.9 vs. 23.5 ± 8.4 % total energy intake) than participants not reporting diabetes.People with diabetes eat less simple carbohydrates, but do not comply with current advice on fish, nuts, fruits and vegetables. Improvement of the dietary intake in persons with diabetes in Switzerland is needed.
Keywords: Diabetes; Dietary composition; Dietary management; Sugar; Artificial sweeteners; Cross-sectional study; Switzerland

Dietary patterns in weight loss maintenance: results from the MedWeight study by Eleni Karfopoulou; Dora Brikou; Eirini Mamalaki; Fragiskos Bersimis; Costas A. Anastasiou; James O. Hill; Mary Yannakoulia (991-1002).
The dietary habits contributing to weight loss maintenance are not sufficiently understood. We studied weight loss maintainers in comparison with regainers, to identify the differentiating behaviors.The MedWeight study is a Greek registry of weight loss maintainers and regainers. Participants had intentionally lost ≥10 % of their weight and either had maintained this loss for over a year, or had regained weight. Questionnaires on demographics and lifestyle habits were completed online. Dietary assessment was carried out by two telephone 24-h recalls.Present analysis focused on 361 participants (32 years old, 39 % men): 264 maintainers and 97 regainers. Energy and macronutrient intake did not differ by maintenance status (1770 ± 651 kcal in maintainers vs. 1845 ± 678 kcal in regainers, p = 0.338), although protein intake per kg of body weight was higher in maintainers (1.02 ± 0.39 vs. 0.83 ± 0.28 g/kg in regainers, p < 0.001). Physical activity energy expenditure was greater for maintainers in men (by 1380 kcal per week, p = 0.016), but not women. Salty snacks, alcohol and regular soda were more frequently consumed by men regainers. Principal component analysis identified a healthy dietary pattern featuring mainly unprocessed cereal, fruit, vegetables, olive oil and low-fat dairy. Male maintainers were 4.6 times more likely to follow this healthy pattern compared to regainers (OR 4.6, 95 % CI 2.0–11.0). No similar finding was revealed in women. Other characteristics of maintainers but not of regainers were: involvement in meal preparation and eating at home for men, and a higher eating frequency and slower eating rate for women.Men maintaining weight loss were much more likely to adhere to a healthy eating pattern. Eating at home, involvement in meal preparation, higher eating frequency and slower eating rate were also associated with maintenance. These lifestyle habits of successful maintainers provide target behaviors to improve obesity treatment.
Keywords: Weight loss maintenance; Maintainers; Regainers; Dietary patterns

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats by Rafael Longhi; Roberto Farina Almeida; Letiane Machado; Maria Marta Medeiros Frescura Duarte; Débora Guerini Souza; Priscila Machado; Adriano Martimbianco de Assis; André Quincozes-Santos; Diogo Onofre Souza (1003-1016).
Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats.Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed.Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets.Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.
Keywords: Obesity; Hydrogenated vegetable oils; Proinflammatory; Brain function

Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study by J. B. Ernst; A. Zittermann; S. Pilz; M. E. Kleber; H. Scharnagl; V. M. Brandenburg; W. König; T. B. Grammer; W. März (1017-1024).
Anemia and vitamin D deficiency are both frequent in adult patients. Whether low vitamin D metabolite levels are an independent risk factor for different subtypes of anemia remains to be studied in detail.In 3299 patients referred for coronary angiography, we investigated the association of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D] with anemia [hemoglobin (Hb) <12.5 g/dl] of specific subtypes.Compared with patients with 25OHD levels in the adequate range (50–125 nmol/l), patients with deficient 25OHD concentrations (<30 nmol/l; 33.6 % of patients) had 0.6 g/dl lower Hb levels. Hb values were 1.3 g/dl lower in patients with 1,25(OH)2D levels <40 pmol/l (5.4 % of patients), compared with patients in the highest 1,25(OH)2D category (>70 pmol/l). Of the participants, 16.7 % met the criteria for anemia. In multivariate-adjusted regression analyses, the odds ratios for anemia in the lowest 25OHD and 1,25(OH)2D categories were 1.52 (95 % CI 1.15–2.02) and 3.59 (95 % CI 2.33–5.52), compared with patients with 25OHD levels in the adequate range and patients with 1,25(OH)2D levels >70 pmol/l. The probability of anemia was highest in patients with combined 25OHD and 1,25(OH)2D deficiency [multivariable-adjusted odds ratio 5.11 (95 % CI 2.66–9.81)]. Patients with anemia of chronic kidney disease had the highest prevalence of 25OHD deficiency and 1,25(OH)2D concentrations of <40 pmol/l.Low 25OHD and 1,25(OH)2D concentrations are independently associated with anemia. Patients with poor kidney function are most affected. Interventional trials are warranted to prove whether administration of plain or activated vitamin D can prevent anemia.
Keywords: 25-Hydroxyvitamin D; 1,25-Dihydroxyvitamin D; Anemia subtypes; Hemoglobin; Coronary angiography

Do dry roasting, lightly salting nuts affect their cardioprotective properties and acceptability? by Siew Ling Tey; Terryn Robinson; Andrew R. Gray; Alexandra W. Chisholm; Rachel Clare Brown (1025-1036).
Previous studies have reported improvements in cardiovascular disease (CVD) risk factors with the consumption of raw nuts. However, around one-third of nuts consumed are roasted and salted. Thus, it is important to determine whether roasting and salting nuts affect the health benefits observed with raw nuts. This study aimed to compare the effects of consuming two different forms of hazelnuts on cardiovascular risk factors and acceptance.Using a randomised crossover design, 72 participants were asked to consume 30 g/day of either raw or dry roasted, lightly salted hazelnuts for 28 days each. CVD risk factors were measured at the beginning and end of each treatment period. “Desire to consume” and “overall liking” for both forms of hazelnuts were assessed daily using a 150-mm visual analogue scale.Body composition, blood pressure, plasma total and low-density lipoprotein-cholesterol, apolipoprotein A1 and B100, glucose and α-tocopherol concentrations did not differ between forms of hazelnuts (all P ≥ 0.054). High-density lipoprotein (HDL)-cholesterol (P = 0.037) and triacylglycerol (P < 0.001) concentrations were significantly lower following the consumption of dry roasted, lightly salted hazelnuts when compared to the raw hazelnuts. Compared with baseline, consuming both forms of hazelnuts significantly improved HDL-cholesterol and apolipoprotein A1 concentrations, total-C/HDL-C ratio, and systolic blood pressure without significantly changing body composition. Acceptance ratings did not differ between forms of hazelnuts and remained high throughout the study.Dry roasting and lightly salting nuts do not appear to negate the cardioprotective effects observed with raw nut consumption, and both forms of nuts are resistant to monotony. Public health messages could be extended to include dry roasted and lightly salted nuts as part of a heart healthy diet.
Keywords: Hazelnuts; Roasting; Salting; Cardiovascular disease; Acceptance

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women by Virginia Govoni; Thomas A. B. Sanders; Dianne P. Reidlinger; Julia Darzi; Sarah E. E. Berry; Louise M. Goff; Paul T. Seed; Philip J. Chowienczyk; Wendy L. Hall (1037-1044).
Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet).A 12-week randomized controlled trial in men and women aged 40–70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density).Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control.Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at as ISRCTN92382106.
Keywords: Dietary guidelines; Cardiovascular disease; Microcirculation; Capillaroscopy; Blood pressure; Randomized controlled trial

Telomere length is a biomarker for aging. It is known that oxidative stress can accelerate telomere shortening, whereas antioxidants can delay their shortening. Carotenoids as antioxidants are favorably associated with health- and aging-related diseases caused by oxidative stress, but their association with telomere length is less certain. We investigated the association between blood carotenoid levels and leukocyte telomere length in a representative sample of US adults.We analyzed 3660 participants aged 20 years and older in the 1999–2002 National Health and Nutrition Examination Survey. The levels of carotenoids—alpha-carotene, beta-carotene (trans + cis), beta-cryptoxanthin, combined lutein/zeaxanthin, and trans-lycopene—were measured using high-performance liquid chromatography. The leukocyte telomere length (T/S ratio) was assayed using the quantitative polymerase chain reaction method.A doubling of blood alpha-carotene, beta-carotene (trans + cis), and beta-cryptoxanthin was associated with approximately 2 % longer telomeres. Compared with the lowest carotenoid quartile of alpha-carotene, beta-carotene (trans + cis), and beta-cryptoxanthin, telomere length for adults with the highest quartiles was significantly increased by 5–8 %.We found that increasing levels of blood carotenoid were significantly associated with longer leukocyte telomeres in US adults. High intake of carotenoid-rich food may play a role in protecting telomeres and regulating telomere length.
Keywords: Telomere; Oxidative stress; Carotenoid; Antioxidant

Effect of meal composition on postprandial glucagon-like peptide-1, insulin, glucagon, C-peptide, and glucose responses in overweight/obese subjects by Meena Shah; Brian Franklin; Beverley Adams-Huet; Joel Mitchell; Brooke Bouza; Lyn Dart; Melody Phillips (1053-1062).
Glucagon-like peptide-1 (GLP-1), an incretin hormone, is released in response to food intake. It is unclear how meals high in protein (HP) and monounsaturated fat (HMF) affect GLP-1 response.To examine the effect of a HP versus a HMF meal on GLP-1 response.Twenty-four overweight/obese participants consumed two meals (HP: 31.9 % energy from protein; HMF: 35.2 % fat and 20.7 % monounsaturated fat) in a random order. Both meals contained the same energy and carbohydrate content. GLP-1, insulin, glucagon, C-peptide, and glucose were assessed from blood drawn in the fasting and postprandial states. The effect of meal condition on hormone and glucose responses and appetite ratings were assessed by repeated measures analysis.Statistically significant (p < 0.01) time by meal condition effect was observed on active GLP-1, total GLP-1, insulin, C-peptide, and glucagon, but not glucose (p = 0.83). Area under the curve was significantly higher during the HP versus the HMF meal conditions for active GLP-1 (23.7 %; p = 0.0007), total GLP-1 (12.2 %; p < 0.0001), insulin (54.4 %; p < 0.0001), C-peptide (14.8 %; p < 0.0001), and glucagon (40.7 %; p < 0.0001). Blood glucose was not different between the HP versus HMF conditions (−4.8 %; p = 0.11). Insulin sensitivity was higher during the HMF versus HP conditions (Matsuda index mean difference: 16.3 %; p = 0.007). Appetite ratings were not different by meal condition.GLP-1 and insulin responses were higher during the HP condition. However, no difference was found in blood glucose between conditions, and insulin sensitivity was higher during the HMF condition, indicating that a HMF meal may be optimal at regulating blood glucose in overweight/obese individuals without type 2 diabetes.
Keywords: High-monounsaturated fat meal; High-protein meal; Meal composition; Glucagon-like peptide-1; Insulin; Obesity

Difference in postprandial GLP-1 response despite similar glucose kinetics after consumption of wheat breads with different particle size in healthy men by Coby Eelderink; Martijn W. J. Noort; Nesli Sozer; Martijn Koehorst; Jens J. Holst; Carolyn F. Deacon; Jens F. Rehfeld; Kaisa Poutanen; Roel J. Vonk; Lizette Oudhuis; Marion G. Priebe (1063-1076).
Underlying mechanisms of the beneficial health effects of low glycemic index starchy foods are not fully elucidated yet. We varied the wheat particle size to obtain fiber-rich breads with a high and low glycemic response and investigated the differences in postprandial glucose kinetics and metabolic response after their consumption.Ten healthy male volunteers participated in a randomized, crossover study, consuming 13C-enriched breads with different structures; a control bread (CB) made from wheat flour combined with wheat bran, and a kernel bread (KB) where 85 % of flour was substituted with broken wheat kernels. The structure of the breads was characterized extensively. The use of stable isotopes enabled calculation of glucose kinetics: rate of appearance of exogenous glucose, endogenous glucose production, and glucose clearance rate. Additionally, postprandial plasma concentrations of glucose, insulin, glucagon, incretins, cholecystokinin, and bile acids were analyzed.Despite the attempt to obtain a bread with a low glycemic response by replacing flour by broken kernels, the glycemic response and glucose kinetics were quite similar after consumption of CB and KB. Interestingly, the glucagon-like peptide-1 (GLP-1) response was much lower after KB compared to CB (iAUC, P < 0.005). A clear postprandial increase in plasma conjugated bile acids was observed after both meals.Substitution of 85 % wheat flour by broken kernels in bread did not result in a difference in glucose response and kinetics, but in a pronounced difference in GLP-1 response. Thus, changing the processing conditions of wheat for baking bread can influence the metabolic response beyond glycemia and may therefore influence health.
Keywords: Glucagon-like peptide-1; Glycemic index; Glucose kinetics; Bile acids; Wheat kernels; Bread processing

Effect of oleic acid on store-operated calcium entry in immune-competent cells by Celia Carrillo; María Giraldo; M. Mar Cavia; Sara R. Alonso-Torre (1077-1084).
To study the mechanism by which oleic acid (OA) (C18:1) exerts its beneficial effects on immune-competent cells. Since store-operated Ca2+ entry (SOCE) is a Ca2+ influx pathway involved in the control of multiple physiological processes including cell proliferation, we studied the effect of OA in Ca2+ signals of Jurkat T cells and THP-1 monocytes, paying particular attention to SOCE.Changes in [Ca2+]i were measured using the Fura-2 fluorescence dye. Mn2+ uptake was monitored as a rate of quenching of Fura-2 fluorescence measured at the Ca2+-insensitive wavelengths. Thapsigargin was used to induce SOCE in Fura-2-loaded cells.We showed a clear dose-dependent SOCE-inhibitory effect of OA in both cell lines. Such an inhibitory effect was PKC independent and totally restored by albumin, suggesting that OA exerts its effect somewhere in the membrane. We also demonstrated that OA induces increases in [Ca2+]i partly mediated by an extracellular Ca2+ influx through econazole-insensitive channels. Finally, we compared the effect of OA with stearic acid (C18:0), assuming the emerged evidence concerning the link between saturated fats and inflammation disorders. Stearic acid failed to inhibit SOCE, independently on the concentration tested, thus intensifying the physiological relevance of our findings.We suggest a physiological pathway for the beneficial effects of OA in inflammation.
Keywords: Oleic acid; Ca2+ signals; SOCE; Immune-competent cells

Chronic inflammation is associated with increased risk of cancer, cardiovascular disease (CVD), and diabetes. The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear. We examined the relationship between diet-associated inflammation, as measured by dietary inflammatory index (DII) score, and mortality, with special focus on prediabetics. This prospective cohort study used data from the Third National Health and Nutrition Examination Survey (NHANES III). We categorized 13,280 eligible participants, ages 20–90 years, according to glycosylated hemoglobin (HgbA1c) level and identified 2681 with prediabetes, defined as a glycosylated hemoglobin percentage of 5.7–6.4. Computation of DII scores and all statistical analyses were conducted in 2015. The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls (1988–1994). Mortality was determined from the National Death Index records through 2006. Over follow-up ranging between 135 and 168 person-months, a total of 3016 deaths were identified, including 676 cancer, 192 lung cancer, 176 digestive-tract cancer, and 1328 CVD deaths. Cox proportional hazard regression was used to estimate hazard ratios.The prevalence of prediabetes was 20.19 %. After controlling for age, sex, race, HgbA1c, current smoking, physical activity, BMI, and systolic blood pressure, DII scores in tertile III (vs tertile I) was significantly associated with mortality from all causes (HR 1.39, 95 % CI 1.13, 1.72), CVD (HR 1.44, 95 % CI 1.02, 2.04), all cancers (HR 2.02, 95 % CI 1.27, 3.21), and digestive-tract cancer (HR 2.89, 95 % CI 1.08, 7.71). Findings for lung cancer (HR 2.01, 95 % CI 0.93, 4.34) suggested a likely effect. These results were moderately enhanced after additional adjustment for serum low-density lipoprotein and triglyceride and following eliminating deaths during the first year.A pro-inflammatory diet, as indicated by higher DII scores, is associated with an increased risk of all-cause, CVD, all-cancer, and digestive-tract cancer mortality among prediabetic subjects.
Keywords: Cancer; Digestive-tract cancers; Cardiovascular disease; Mortality; Dietary inflammatory index; Diet; Inflammation; HgbA1c; Prospective study

Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials by Azizah Mat Hussin; Ammar W. Ashor; Inez Schoenmakers; Tom Hill; John C. Mathers; Mario Siervo (1095-1104).
In addition to regulating calcium homoeostasis and bone health, vitamin D influences vascular and metabolic processes including endothelial function (EF) and insulin signalling. This systematic review and meta-analysis of randomised clinical trials (RCTs) were conducted to investigate the effect of vitamin D supplementation on EF and to examine whether the effect size was modified by health status, study duration, dose, route of vitamin D administration, vitamin D status (baseline and post-intervention), body mass index (BMI), age and type of vitamin D.We searched the Medline, Embase, Cochrane Library and Scopus databases from inception until March 2015 for studies meeting the following criteria: (1) RCT with adult participants, (2) vitamin D administration alone, (3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography, applanation tonometry and laser Doppler. Sixteen articles reporting data for 1177 participants were included. Study duration ranged from 4 to 52 weeks. The effect of vitamin D on EF was not significant (SMD: 0.08, 95 % CI −0.06, 0.22, p = 0.28). Subgroup analysis showed a significant improvement of EF in diabetic subjects (SMD: 0.31, 95 % CI 0.05, 0.57, p = 0.02). A non-significant trend was found for diastolic blood pressure (β = 0.02; p = 0.07) and BMI (β = 0.05; p = 0.06).Vitamin D supplementation did not improve EF. The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function. This remains to be tested in future studies.
Keywords: Vitamin D; Nitric oxide; Flow-mediated dilation; Forearm blood flow; Pulse wave velocity; Cardiovascular risk

A nutrient profiling system for the (re)formulation of a global food and beverage portfolio by Antonis Vlassopoulos; Gabriel Masset; Veronique Rheiner Charles; Cassandra Hoover; Caroline Chesneau-Guillemont; Fabienne Leroy; Undine Lehmann; Jörg Spieldenner; E-Siong Tee; Mike Gibney; Adam Drewnowski (1105-1122).
To describe the Nestlé Nutritional Profiling System (NNPS) developed to guide the reformulation of Nestlé products, and the results of its application in the USA and France.The NNPS is a category-specific system that calculates nutrient targets per serving as consumed, based on age-adjusted dietary guidelines. Products are aggregated into 32 food categories. The NNPS ensures that excessive amounts of nutrients to limit cannot be compensated for by adding nutrients to encourage. A study was conducted to measure changes in nutrient profiles of the most widely purchased Nestlé products from eight food categories (n = 99) in the USA and France. A comparison was made between the 2009–2010 and 2014–2015 products.The application of the NNPS between 2009–2010 and 2014–2015 was associated with an overall downwards trend for all nutrients to limit. Sodium and total sugars contents were reduced by up to 22 and 31 %, respectively. Saturated Fatty Acids and total fat reductions were less homogeneous across categories, with children products having larger reductions. Energy per serving was reduced by <10 % in most categories, while serving sizes remained unchanged.The NNPS sets feasible and yet challenging targets for public health-oriented reformulation of a varied product portfolio; its application was associated with improved nutrient density in eight major food categories in the USA and France. Confirmatory analyses are needed in other countries and food categories; the impact of such a large-scale reformulation on dietary intake and health remains to be investigated.
Keywords: Nutrition; Foods; Nutrient profiling; Reformulation

Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia by Delphine Casabonne; Esther Gracia; Ana Espinosa; Mariona Bustamante; Yolanda Benavente; Claudia Robles; Laura Costas; Esther Alonso; Eva Gonzalez-Barca; Adonina Tardón; Trinidad Dierssen-Sotos; Eva Gimeno Vázquez; Marta Aymerich; Elies Campo; José J. Jiménez-Moleón; Rafael Marcos-Gragera; Gemma Castaño-Vinyals; Nuria Aragones; Marina Pollan; Manolis Kogevinas; Carmen Urtiaga; Pilar Amiano; Victor Moreno; Silvia de Sanjose (1123-1133).
There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic variability in vitamin C transporter gene SLC23A2 could explain some inconsistencies in the literature.Fruit/vegetable/vitamin C consumption from food frequency questionnaires and six low-penetrance genetic susceptibility polymorphisms in vitamin C transporter gene SLC23A2 (rs1715364, rs6133175, rs1776948, rs6139587, rs369270 and rs6052937) were examined in 434 CLL cases and 1257 randomly selected controls from primary care centres with genetic data of whom 275 cases and 1094 controls having both diet and genetic information. Logistic regression models were used to estimate odds ratio (OR) and 95 % confidence intervals (CI).CLL patients were more likely to have a higher fruit consumption than controls (highest versus lowest quartile in g/day OR: 1.48; 95 % CI: 1.00 to 2.18; P = 0.03), whereas no associations were found with vegetable or total vitamin C intake. Based on log-additive models, rs6133175_A > G (OR: 1.19, 95 % CI: 1.00 to 1.41; P = 0.05) and rs1776948_T > A (OR: 1.20; 95 %CI: 1.01 to 1.41; P = 0.04) were associated with CLL. The haplogenotype analysis (rs1715364, rs6133175) supported the genotype results. No gene–diet interactions in CLL remained statistically significant after correction for multiple testing.These data suggest that both fruit intake and genetic marker in SLC23A2 may play an independent role in CLL biology.
Keywords: Fruit intake; Vegetable intake; Vitamin C intake; SLC23A2; Polymorphism; Chronic lymphocytic leukaemia

The industrially produced partially hydrogenated vegetable fat (PHVF) contains trans fatty acid mostly comprising of elaidic acid (18:1 ∆9t). PHVF is used as a cooking medium in Southeast Asian countries. The purpose of this study is to evaluate the effects of dietary PHVF on inflammatory mediators and possible ameliorative effects of n-3 fatty acid (α-linolenic acid, ALA)-rich linseed oil (LSO) on the inflammatory mediators. Male Wistar weaning rats were fed AIN-93-purified diet supplemented with one of the following lipids for 60 days, groundnut oil (GNO, 10 wt%), PHVF (10 wt%), LSO (10 wt%), PHVF blended with LSO at 2.5, 5.0 and 7.5 wt% levels. The final fat level in the diet was maintained at 10 wt%.The macrophages from rats fed PHVF showed higher levels of total cholesterol and free cholesterol as compared to those from rats fed GNO and LSO. Macrophages from rats fed PHVF down-regulated the expression of PPARγ and up-regulated the expressions of cytosolic phospholipase A2, cyclooxygenase-2, 5-lipoxygenase and nuclear factor-kappa B p65. The macrophages from rats fed PHVF secreted higher levels of pro-inflammatory eicosanoids and cytokines. The rats fed PHVF blended with LSO at incremental amounts showed a significant reduction in the expressions of pro-inflammatory markers in dose-dependent manner.Detrimental effects of dietary PHVF in enhancing pro-inflammatory agents in rats could be significantly reduced by providing ALA (n-3 PUFA)-rich LSO.
Keywords: Partially hydrogenated vegetable fat; Elaidic acid; Linseed oil; α-Linolenic acid; Macrophages; Inflammatory mediators

Elevated urinary Na/K ratio among Lebanese elementary school children is attributable to low K intake by Carla El Mallah; Karina Merhi; Hala Ghattas; Dareen Shatila; Sirine Francis; Sani Hlais; Imad Toufeili; Omar Obeid (1149-1156).
To estimate total sodium (Na) and potassium (K) intake using non-fasting morning urine specimens among Lebanese elementary (6–10 year old) schoolchildren.A national cross-sectional study was conducted. A multistage cluster sampling procedure was used to select a representative sample of 1403 healthy children from the eight districts of Lebanon. Age, anthropometric measurements, and urine samples were collected and analyzed for Na, K, and creatinine (Cr).The ratios of Na and K to Cr were 23.93 ± 15.54 mM/mM (4.86 ± 3.16 mg/mg) and 11.48 ± 5.82 mM/mM (3.97 ± 2.01 mg/mg), respectively, and showed differences (P value <0.001) between age groups. No differences were found between boys and girls in all the measured Na and K parameters. The estimated mean Na intake was 96.57 ± 61.67 mM/day (2.220 ± 1.418 g/day or 5.69 ± 3.64 g NaCl/day) and exceeded the upper limit of intake in half the children. Estimated K intake was 46.6 ± 23.02 mM/day (1.822 ± 0.900 g/day), and almost all children failed to meet the recommended daily K intake. The high Na/K ratio (2.361 ± 1.67 mM/mM or 1.39 ± 0.98 mg/mg) resulted from a combination of high Na and low K intake but was mostly affected by K intake.About 50 % of children exceeded the recommended daily upper intake for Na, while the majority was below K adequate intake. This unfavorable Na/K ratio is indicative of potentially negative health effects at later stages in life. Interventions aimed at reducing salt intake and increasing consumption of fruits and vegetables are warranted.
Keywords: Lebanese children; Potassium intake; Sodium intake; Urinary potassium-to-creatinine ratio; Urinary sodium-to-creatinine ratio

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort by Mireia Obón-Santacana; Leila Lujan-Barroso; Heinz Freisling; Claire Cadeau; Guy Fagherazzi; Marie-Christine Boutron-Ruault; Rudolf Kaaks; Renée T. Fortner; Heiner Boeing; J. Ramón Quirós; Esther Molina-Montes; Saioa Chamosa; José María Huerta Castaño; Eva Ardanaz; Kay-Tee Khaw; Nick Wareham; Tim Key; Antonia Trichopoulou; Pagona Lagiou; Androniki Naska; Domenico Palli; Sara Grioni; Rosario Tumino; Paolo Vineis; Maria Santucci De Magistris; H. B. Bueno-de-Mesquita; Petra H. Peeters; Maria Wennberg; Ingvar A. Bergdahl; Hubert Vesper; Elio Riboli; Eric J. Duell (1157-1168).
Acrylamide was classified as ‘probably carcinogenic’ to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th–75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8–53.1) pmol/g Hb and 34.2 (25.4–46.9) pmol/g Hb, respectively.The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively.Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.
Keywords: Acrylamide; Glycidamide; Hemoglobin adducts; Biomarkers; Diet; Nutrition

Association between dietary carbohydrate intake, glycemic index and glycemic load, and risk of gastric cancer by Yao Ye; Yihua Wu; Jinming Xu; Kefeng Ding; Xiaoyun Shan; Dajing Xia (1169-1177).
The association between dietary carbohydrate intake, glycemic index (GI) and glycemic load (GL), and risk of gastric cancer (GC) has been investigated by many studies. However, the results of these studies were controversial. The aim of our study was to systematically assess this issue.PUBMED and EMBASE were searched up to March 2015, and either a fixed- or a random-effects model was adopted to estimate overall relative risks (RRs). Dose–response, meta-regression, subgroup, and publication bias analyses were applied.Twenty-six studies with approximately 540,000 participants were finally included in this meta-analysis. High level of dietary carbohydrate intake (pooled RR 1.17, 95 % CI 0.91–1.50), GI (pooled RR 1.17, 95 % CI 0.80–1.69), and GL (pooled RR 1.06, 95 % CI 0.90–1.26) were all nonsignificantly associated with incidence of GC. In addition, no significant dose–response relationship was observed between carbohydrate intake, GI and GL, and the risk of GC. However, further subgroup analyses based on gender and geographic region suggested a significant association between higher carbohydrate intake (pooled RR 1.52, 95 % CI 1.10–2.08), GL (pooled RR 1.41, 95 % CI 1.04–1.92), and GC risk in males subgroup, and between higher carbohydrate intake (pooled RR 1.69, 95 % CI 1.36–2.09) and GC risk in Asian studies.No significant association was found between dietary carbohydrate intake, GI and GL, and risk of GC. However, significantly positive association was observed in the males subgroup and Asian studies.
Keywords: Carbohydrate intake; Glycemic index; Glycemic load; Gastric cancer

Associations of dietary diversity scores and micronutrient status in adolescent Mozambican girls by Liisa Korkalo; Maijaliisa Erkkola; Arja E. Heinonen; Riitta Freese; Kerry Selvester; Marja Mutanen (1179-1189).
In low-income settings, dietary diversity scores (DDSs) often predict the micronutrient adequacy of diets, but little is known about whether they predict levels of biochemical indicators of micronutrient status. In 2010, we studied two samples of non-pregnant 14- to 19-year-old girls in central Mozambique, the first in January–February (‘hunger season’; n = 227) and the second in May–June (harvest season; n = 223). In this paper, we examined whether a low Women’s Dietary Diversity Score (WDDS) predicts a low concentration of haemoglobin, serum ferritin, zinc, and folate, and plasma retinol in adolescent Mozambican girls. We constructed three scores: WDDS based on 24-h recalls, WDDS15g based on 24-h recall and employing a 15 g limit, and 7dWDDS based on 7-day food frequency questionnaires. Logistic regression models, stratified by season, were used to estimate the odds of having a low concentration of a status indicator (≤25th percentile of the season-specific distribution or cut-off from the literature) in those with a low score compared to those with a higher score.In January–February, after adjusting for confounders, a low (≤3) WDDS and a low (≤5) 7dWDDS were each associated with higher odds of having low serum zinc compared to having a higher score, regardless of which of the two types of cut-offs for serum zinc was used. These associations were not present in May–June.Our data from Mozambique suggest that dietary diversity is associated with serum zinc, but this association seems to be limited to the hunger season.
Keywords: Dietary diversity score; Micronutrient; Nutritional status; Adolescent girl; Mozambique; Sub-Saharan Africa

A khorasan wheat-based replacement diet improves risk profile of patients with type 2 diabetes mellitus (T2DM): a randomized crossover trial by Anne Whittaker; Monica Dinu; Francesca Cesari; Anna Maria Gori; Claudia Fiorillo; Matteo Becatti; Alessandro Casini; Rossella Marcucci; Stefano Benedettelli; Francesco Sofi (1191-1200).
The aim of the present study was to examine whether a replacement diet with products made with organic ancient khorasan wheat could provide additive protective effects in reducing glucose, insulin, lipid and inflammatory risk factors, and in restoring blood redox balance in type 2 diabetes mellitus (T2DM) patients compared to diet with product made with modern organic wheat.We conducted a randomized, double-blinded crossover trial with two intervention phases on 21 T2DM patients (14 females, 7 males). The participants were assigned to consume products (bread, pasta, crackers and biscuits) made using semi-whole flour from organic wheat that was either from ancient khorasan wheat or modern control wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Laboratory analyses were performed both at the beginning and at the end of each intervention phase.The metabolic risk profile improved only after the khorasan intervention period, as measured by a reduction in total and LDL cholesterol (mean reduction: −3.7 and −3.4 %, respectively), insulin (−16.3 %) and blood glucose (−9.1 %). Similarly, there was a significant reduction in circulating levels of reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and interleukin-1ra, and a significant increase of total antioxidant capacity (+6.3 %). No significant differences from baseline were noted after the modern control wheat intervention phase. The change (from pre- to post-intervention) between the two intervention arms was significantly different (p < 0.05) for total and LDL-c, insulin and HOMA index.A replacement diet with ancient khorasan wheat consumption provided additive protection in reducing total and LDL cholesterol, insulin, blood glucose, ROS production, and some inflammatory risk factors, which are all key factors warranting of control in secondary prevention of T2DM compared to a diet with products made with modern wheat.
Keywords: Organic wheat; Ancient wheat; Modern wheat; Khorasan wheat; Type 2 diabetes mellitus; Secondary prevention; Glycaemia; Oxidative stress; Inflammation cytokines

Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats by Ilma Cely de Amorim Ribeiro; Carlos Alberto Soares da Costa; Vivian Alves Pereira da Silva; Lanna Beatriz Neves Silva Côrrea; Gilson Teles Boaventura; Mauricio Alves Chagas (1201-1210).
This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli.The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated.These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.
Keywords: Prostate; Rats; Benign prostatic hyperplasia; Diet; Flaxseed

The effect of hypohydration on endothelial function in young healthy adults by Giannis Arnaoutis; Stavros A. Kavouras; Nikolaos Stratakis; Marita Likka; Asimina Mitrakou; Christos Papamichael; Labros S. Sidossis; Kimon Stamatelopoulos (1211-1217).
Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function.Ten young, healthy males participated in this crossover study (age: 24.3 ± 2.3 year; weight: 80.8 ± 5.3 kg; BMI: 24.3 ± 0.4 kg m−2). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low-intensity intermittent walking exercise to achieve hypohydration of −2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded.Hypohydration by −1.9 ± 0.1 % of body mass resulted in decreased plasma volume by −3.5 ± 1.8 % and increased plasma osmolality by 9 ± 2 mmol kg−1 (P < 0.001). FMD as a response to hypohydration decreased by −26.8 ± 3.9 % (P < 0.05).The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function.
Keywords: Dehydration; Endothelial; Flow-mediated dilation; Fluid balance; Cardiovascular disease

The role of fortified foods and nutritional supplements in increasing vitamin D intake in Irish preschool children by Áine Hennessy; Fiona Browne; Mairead Kiely; Janette Walton; Albert Flynn (1219-1231).
There are limited data on the contribution of fortified foods and nutritional supplements to intakes of vitamin D in young children. Our objective was to examine the intake, adequacy, risk of excessive intake and sources of dietary vitamin D. The nationally representative cross-sectional dietary survey of young children (aged 1–4 years) (n 500) was used to evaluate vitamin D intake and quantify the contribution of the base diet, fortified foods and nutritional supplements to total intake.Median (IQR) intakes of vitamin D were generally low in this young population, ranging from 2.0 (1.9) to 2.5 (4.9) µg/day. Ninety-three and 78 % of children had intakes below 10 and 5 µg/day, respectively. While vitamin D supplement users (17 %) had the highest intakes [6.7 (6.4) µg/day] (P < 0.001), 74 % had intakes below 10 µg/day. Vitamin D-fortified foods, consumed by 77 % of children [2.2 (2.0) µg/day], made nutritionally significant contributions to intake [0.8 (1.6) µg/day], particularly in younger children [1.5 (4.6) µg/day]. Children who did not use nutritional supplements or fortified foods had significantly (P < 0.001) lower intakes of vitamin D than the other groups [1.0 (0.8) µg/day]. Our analyses show the importance of milk and yoghurt, meat and fortified ready-to-eat cereals as sources of vitamin D in this age group. The use of nutritional supplements or fortified foods at current levels does not represent a risk of intakes exceeding the European Food Safety Authority (EFSA) tolerable upper intake level (UL) (50 µg/day), as intakes did not exceed or even approach the UL (P95: 22 % of UL).Intakes of vitamin D in preschool children in Ireland are generally low. Nutritional supplements and fortified foods make significant contributions to intakes of vitamin D, without risk of unacceptably high intakes. Though supplements are effective in raising intakes of vitamin D in users, uptake is low (17 %). Food fortification may represent a suitable public health approach to increasing vitamin D intakes. The national food consumption data of Irish preschool children provide the ideal starting point for modelling of fortification scenarios to identify which foods and levels of addition will ensure effective and safe increases in vitamin D intake.
Keywords: Vitamin D; Preschool children; Fortified foods; Nutritional supplements; Adequacy; Excessive intake

Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study by Nadia Bastide; Laureen Dartois; Valérie Dyevre; Laure Dossus; Guy Fagherazzi; Mauro Serafini; Marie-Christine Boutron-Ruault (1233-1243).
The cellular oxidative stress (balance between pro-oxidant and antioxidant) may be a major risk factor for chronic diseases. Antioxidant capacity of human diet can be globally assessed through the dietary non-enzymatic antioxidant capacity (NEAC). Our aim was to investigate the relationship between the NEAC and all-cause and cause-specific mortality, and to test potential interactions with smoking status, a well-known pro-oxidant factor.Among the French women of the E3N prospective cohort study initiated in 1990, including 4619 deaths among 1,199,011 persons-years of follow-up. A validated dietary history questionnaire assessed usual food intake; NEAC intake was estimated using a food composition table from two different methods: ferric ion reducing antioxidant power (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hazard ratio (HR) estimates and 95 % confidence intervals (CI) were derived from Cox proportional hazards regression models.In multivariate analyses, FRAP dietary equivalent intake was inversely associated with mortality from all-causes (HR for the fourth vs. the first quartile: HR4 = 0.75, 95 % CI 0.67, 0.83, p trend < 0.0001), cancer, and cardiovascular diseases. Similar results were obtained with TRAP. There was an interaction between NEAC dietary equivalent intake and smoking status for all-cause and cardiovascular disease mortality, but not cancer mortality (respectively, for FRAP, p inter = 0.002; 0.013; 0.113, results were similar with TRAP), and the association was the strongest among current smokers.This prospective cohort study highlights the importance of antioxidant consumption for mortality prevention, especially among current smokers.
Keywords: Non-enzymatic antioxidant capacity; FRAP; TRAP; All-cause and cause-specific mortality; E3N study

The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans by Tom Clifford; Costas M. Constantinou; Karen M. Keane; Daniel J. West; Glyn Howatson; Emma J. Stevenson (1245-1254).
To evaluate the plasma bioavailability of betanin and nitric oxide (NOx) after consuming beetroot juice (BTJ) and whole beetroot (BF). BTJ and BF were also analysed for antioxidant capacity, polyphenol content (TPC) and betalain content.Ten healthy males consumed either 250 ml of BTJ, 300 g of BF or a placebo drink, in a randomised, crossover design. Venous plasma samples were collected pre (baseline), 1, 2, 3, 5 and 8 h post-ingestion. Betanin content in BTJ, BF and plasma was analysed with reverse-phase high-performance liquid chromatography (HPLC) and mass spectrometry detection (LCMS). Antioxidant capacity was estimated using the Trolox equivalent antioxidant capacity (TEAC) and polyphenol content using Folin–Ciocalteu colorimetric methods [gallic acid equivalents (GAE)] and betalain content spectrophotometrically.TEAC was 11.4 ± 0.2 mmol/L for BTJ and 3.4 ± 0.4 μmol/g for BF. Both BTJ and BF contained a number of polyphenols (1606.9 ± 151 mg/GAE/L and 1.67 ± 0.1 mg/GAE/g, respectively), betacyanins (68.2 ± 0.4 mg/betanin equivalents/L and 19.6 ± 0.6 mg/betanin equivalents/100 g, respectively) and betaxanthins (41.7 ± 0.7 mg/indicaxanthin equivalents/L and 7.5 ± 0.2 mg/indicaxanthin equivalents/100 g, respectively). Despite high betanin contents in both BTJ (~194 mg) and BF (~66 mg), betanin could not be detected in the plasma at any time point post-ingestion. Plasma NOx was elevated above baseline for 8 h after consuming BTJ and 5 h after BF (P < 0.05).These data reveal that BTJ and BF are rich in phytonutrients and may provide a useful means of increasing plasma NOx bioavailability. However, betanin, the major betalain in beetroot, showed poor bioavailability in plasma.
Keywords: Beetroot; Betalains; Nitric oxide; Antioxidant; Bioavailability

Energy compensation and nutrient displacement following regular consumption of hazelnuts and other energy-dense snack foods in non-obese individuals by Katherine R. Pearson; Siew Ling Tey; Andrew R. Gray; Alexandra Chisholm; Rachel C. Brown (1255-1267).
Regular nut consumption reduces cardiovascular disease risk, partly from improvements to dietary quality. Examining how individuals make dietary changes when consuming nuts may reveal key behavioural eating patterns beneficial for the development of dietary interventions. We examined the effects of nuts in comparison with other energy-dense snacks on energy compensation, nutrient displacement, and food group patterns.This was a 12-week randomised, controlled, parallel study with four arms: ~1100 kJ/day for each of hazelnuts (42 g), chocolate (50 g), potato crisps (50 g), or no added snack food. Diet records, body composition, and physical activity were measured at baseline and week 12, in 102 non-obese participants.Significant improvements in diet quality were observed in the hazelnut group, particularly when consumed as snacks. Intakes of monounsaturated fat (MUFA) and vitamin E were significantly higher (all P < 0.05), whereas saturated fat and carbohydrate were significantly lower (both P ≤ 0.022) in the hazelnut group compared to the other groups. Partial energy compensation did not differ significantly between groups, but nutrient displacement values for MUFA and fibre differed significantly. Within the hazelnut group, there was nearly complete displacement for fibre, partial displacement for energy, protein, total fat, MUFA, PUFA, potassium, folate, and vitamin E, and overcompensation for carbohydrate and sugar.Our results demonstrate that energy compensation occurs for all three intervention snacks in this non-obese population. Regular nut consumption significantly improves nutrient profiles compared to other snacks with changes occurring at the snack level.
Keywords: Hazelnuts; Nutrient intake; Nutrient displacement; Energy compensation; Snack

Food sources of dietary sodium in the Japanese adult population: the international study of macro-/micronutrients and blood pressure (INTERMAP) by Nagako Okuda; Akira Okayama; Katsuyuki Miura; Katsushi Yoshita; Shigeyuki Saito; Hideaki Nakagawa; Kiyomi Sakata; Naoko Miyagawa; Queenie Chan; Paul Elliott; Hirotsugu Ueshima; Jeremiah Stamler (1269-1280).
It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study.Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40–59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW).Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P = 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001).Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population.
Keywords: Sodium intake; Food intake; 24-h urine; Japanese diet; Population study

Plasma n-3 polyunsaturated fatty status and its relationship with vitamin E intake and plasma level by Yang Zhao; Frank J. Monahan; Breige A. McNulty; Kaifeng Li; Frederick J. Bloomfield; Daniel J. Duff; Lorraine Brennan; Anne P. Nugent; Eileen R. Gibney (1281-1291).
The aim of the study was to investigate habitual vitamin E intake and plasma α-tocopherol concentration and their relationship with plasma fatty acid profile in a healthy adult population.Vitamin E and fatty acid intake data were determined from the National Adult Nutrition Survey. Plasma α- and γ-tocopherol concentrations were quantified by high-performance liquid chromatography and the percentage of fatty acids in plasma by gas chromatography coupled with mass spectrometry. Participants (n = 601) were divided into vitamin E intake quartiles and plasma α-tocopherol quartiles, and differences in fatty acid intake and plasma fatty acid profile were analyzed by a general linear model.Dietary intake data showed that as vitamin E intake increased, intakes of total polyunsaturated fatty acid (PUFA) and α-linolenic acid increased significantly (p < 0.001), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) did not. After adjusting for fatty acid intake, vitamin E intake was positively related to plasma n-3 PUFA (EPA and DHA) levels and plasma n-3/n-6 PUFA ratio. Plasma α-tocopherol concentration was positively related to the percentage of plasma total PUFA, n-3 PUFA and EPA and inversely related to the percentage of plasma n-6 PUFA.The study illustrates that there are statistical relationships between plasma fatty acid profile and both vitamin E intake and plasma α-tocopherol concentration. Vitamin E may play a role in the maintenance of plasma n-3 PUFA profile in humans with consequent desirable health effects.
Keywords: Polyunsaturated fatty acid; α-Tocopherol; Vitamin E intake; EPA; DHA; n-3/n-6 PUFA ratio

FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk by Norbert Sprenger; Hannah Odenwald; Anna Kaarina Kukkonen; Mikael Kuitunen; Erkki Savilahti; Clemens Kunz (1293-1301).
Manifestation of allergic disease depends on genetic predisposition, diet and commensal microbiota. Genetic polymorphism of mothers determines their breast milk glycan composition. One major determinant is the fucosyltransferase 2 (FUT2, secretor gene) that was shown to be linked to commensal microbiota establishment. We studied whether FUT2-dependent breast milk oligosaccharides are associated with allergic disease in breast-fed infants later in life.We analyzed FUT2-dependent oligosaccharides in breast milk samples of mothers (n = 266) from the placebo group of a randomized placebo-controlled trial of prebiotics and probiotics as preventive against allergic disease in infants with high allergy risk (trial registry number: NCT00298337). Using logistic regression models, we studied associations between FUT2-dependent breast milk oligosaccharides and incidence of allergic disease at 2 and 5 years of age.At 2 years, but not at 5 years of age, we observed a presumed lower incidence (p < 0.1) for IgE-associated eczema manifestation in C-section-born infants who were fed breast milk containing FUT2-dependent oligosaccharides. By logistic regression, we observed a similar relation (p < 0.1) between presence of FUT2-dependent breast milk oligosaccharides and IgE-associated disease and IgE-associated eczema in C-section-born infants only. When testing with the levels of breast milk oligosaccharide 2′-fucosyllactose as proxy for FUT2 activity, we observed significant (p < 0.05) associations in the C-section-born infants with ‘any allergic disease,’ IgE-associated disease, eczema and IgE-associated eczema. The data indicate that infants born by C-section and having a high hereditary risk for allergies might have a lower risk to manifest IgE-associated eczema at 2 years, but not 5 years of age, when fed breast milk with FUT2-dependent milk oligosaccharides. Further studies with larger cohorts and especially randomized controlled intervention trials are required to build on these preliminary observations.
Keywords: Human milk oligosaccharides; Breast-feeding; Allergy; Mode of delivery

Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model by Peter Kubatka; Martin Kello; Karol Kajo; Peter Kruzliak; Desanka Výbohová; Ján Mojžiš; Marián Adamkov; Silvia Fialová; Lucia Veizerová; Anthony Zulli; Martin Péč; Dagmar Statelová; Daniel Grančai; Dietrich Büsselberg (1303-1316).
There has been a considerable interest in the identification of natural plant foods for developing effective agents against cancer. Thus, the anti-tumour effects of oregano in the in vivo and in vitro breast cancer model were evaluated.Lyophilized oregano (ORE) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Moreover, in vitro evaluation in MCF-7 cells was carried out.Low-dose ORE suppressed tumour frequency by 55.5 %, tumour incidence by 44 %, and tumour volume by 44.5 % compared to control animals. Analysis of rat tumour cells showed Ki67, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase after low-dose ORE treatment. High-dose ORE lengthened tumour latency by 12.5 days; moreover, Bcl-2, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase in carcinoma cells were observed. Histopathological analysis revealed a decrease in the ratio of high-/low-grade carcinomas in both treated groups. In vitro studies showed that ORE decreased survival and proliferation of MCF-7 cells. In ORE-treated MCF-7 cells, an increase in cells expressing sub-G 0/G 1 DNA content and an increase in the percentage of annexin V/PI positive MCF-7 cells were observed. In vitro, both caspase-dependent and possible non-caspase-dependent apoptotic pathways were found. The deactivation of anti-apoptotic activity of Bcl-2, a decrease in mitochondrial membrane potential, and the activation of mitochondrial apoptosis pathway were observed in the ORE-treated MCF-7 cells.Our results demonstrate, for the first time, a distinct tumour-suppressive effect of oregano in the breast cancer model.
Keywords: Mammary carcinogenesis; Rat; Oregano; Cancer stem cells; Angiogenesis; Apoptosis; Cell proliferation; MCF-7 cells

Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein by Keita Takahashi; Shoko Takisawa; Kentaro Shimokado; Nozomu Kono; Hiroyuki Arai; Akihito Ishigami (1317-1327).
Despite numerous studies on the RRR- and all-rac-α-tocopherol isoform of vitamin E (VE) during aging, this relationship has not been examined in specific tissues. Since α-tocopherol is the most abundant of VE’s eight isoforms, and VE is an important antioxidant that impacts the aging process, we analyzed α-tocopherol levels in plasma and tissues of mice at progressive ages. Moreover, we examined protein and mRNA expression levels of hepatic α-tocopherol transfer protein (α-TTP), which specifically binds α-tocopherol, during aging.The α-tocopherol levels in plasma, liver, cerebrum, hippocampus, cerebellum, heart, kidney, epididymal adipose tissue, testis, pancreas, soleus muscle, plantaris muscle, and duodenum from male C57BL/6NCr mice at 3, 6, 12, 18, and 24 months of age were determined by HPLC and fluorescence detection. Also, hepatic α-TTP protein and mRNA expression levels were analyzed by Western blot and qPCR, respectively.Tissue-specific, age-related changes of α-tocopherol levels normalized by tissue weight were observed in the liver, cerebrum, hippocampus, cerebellum, heart, kidney, and epididymal adipose tissue. Specifically, α-tocopherol levels in epididymal adipose tissue increased greatly as mice aged from 6 to 24 months. Although hepatic α-TTP protein levels also showed age-related changes, α-TTP mRNA expression levels measured after overnight fasting were not altered.In this study, we determined that α-tocopherol levels and hepatic α-TTP protein levels of mice undergo significant tissue-specific, age-related changes. This is the first report to investigate VE in terms of the α-tocopherol levels in plasma and various tissues of mice and hepatic α-TTP protein levels during aging.
Keywords: Vitamin E; α-Tocopherol; α-Tocopherol transfer protein; Aging; Liver

Serum betaine but not choline is inversely associated with breast cancer risk: a case–control study in China by Yu-Feng Du; Fang-Yu Lin; Wei-Qing Long; Wei-Ping Luo; Bo Yan; Ming Xu; Xiong-Fei Mo; Cai-Xia Zhang (1329-1337).
Choline and betaine are important for DNA methylation and synthesis, and may affect tumor carcinogenesis. To our knowledge, no previous study has examined the association between serum choline and betaine and breast cancer risk. This study aimed to examine whether serum choline and betaine were inversely associated with breast cancer risk among Chinese women.This hospital-based case–control study consecutively recruited 510 breast cancer cases and 518 frequency-matched (age and residence) controls, and blood samples were available for 500 cases and 500 controls. Serum choline and betaine were assayed by high-performance liquid chromatography–tandem mass spectrometry. Multiple unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs).An inverse association with breast cancer risk was observed for serum betaine (fourth vs first quartile adjusted OR 0.68, 95 % CI 0.47–0.97) and for the ratio of serum betaine to choline (fourth vs first quartile adjusted OR 0.70, 95 % CI 0.48–1.00), but not for serum choline (fourth vs first quartile adjusted OR 0.80, 95 % CI 0.56–1.15). Serum betaine was inversely associated with breast cancer risk in subjects with below-median dietary folate intake (fourth vs first quartile adjusted OR 0.48, 95 % CI 0.30–0.77).This study suggested that serum betaine but not choline was inversely associated with breast cancer risk. This result needed to be further confirmed by the prospective studies.
Keywords: Serum choline; Serum betaine; Breast cancer risk; Case–control study

Although it has been suggested that socioeconomic status is associated with dietary quality, the possible mediation effects of eating behaviours on dietary quality are unclear. Thus, we investigated the causal chain by which socioeconomic status influences the quality of the diets consumed by children through their eating behaviours using data from the Korean National Health and Nutrition Examination Survey.The study focused on persons from 2 to 18 years of age who completed the 24-h dietary recall survey (n = 3158). Using causal mediation analysis, we assessed the relationship between socioeconomic status and poor dietary quality in children and examined the mediation effects of eating behaviours. Socioeconomic indicators included household income, parental education, and parental occupation. Dietary quality was defined by the number of key nutrients, protein, calcium, phosphorous, iron, vitamin A, vitamin B1, vitamin B2, niacin, and vitamin C, consumed at insufficient levels.In the present study, more than half the children did not consume the recommended amounts of vitamin A, vitamin C, iron, and calcium. Eating breakfast had a significant impact on poor dietary quality regardless of socioeconomic indicators. On the other hand, children from lower-middle-income households consumed insufficient amounts of more nutrients than their counterparts regardless of eating behaviours. Through the mediation model, we found that lower-middle household incomes were associated with poor dietary quality, but that dietary quality was significantly mediated by eating breakfast.We found that poor dietary quality among children in lower-income households was partially explained by their being less likely to eat breakfast, but that eating breakfast did not entirely mediate these effects. Thus, to reduce differences in dietary quality among children, those who are economically vulnerable must be prioritized.
Keywords: Causal mediation; Children; Dietary quality; Micronutrients

Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial by Verena Brüll; Constanze Burak; Birgit Stoffel-Wagner; Siegfried Wolffram; Georg Nickenig; Cornelius Müller; Peter Langguth; Birgit Alteheld; Rolf Fimmers; Peter Stehle; Sarah Egert (1347-1357).
To determine whether postprandial metabolic and vascular responses induced by a high-fat and high-carbohydrate meal are attenuated by ingestion of the flavonol quercetin.Twenty-two overweight-to-obese hypertensive patients participated in a randomized, double-blind, controlled, crossover meal study. They consumed a test meal (challenge) rich in energy (4754 kJ), fat (61.6 g), saturated fatty acids (53 % of total fatty acids), and carbohydrates (113.3 g) with either placebo or 54 mg quercetin. Blood pressure, reactive hyperemia index (RHI), high-sensitive C-reactive protein (hs-CRP), soluble endothelial-derived adhesion molecules, parameters of lipid and glucose metabolism, and markers of antioxidant status were measured before the meal and at 2 and 4 h postprandially.Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin). During both treatments, serum endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and plasma asymmetric dimethylarginine slightly decreased over time, whereas RHI increased. Serum triglycerides, total cholesterol, and insulin significantly increased, whereas HDL cholesterol and glucose significantly decreased over time, again with no effect of treatment. Plasma α-tocopherol significantly increased, and plasma Trolox equivalent antioxidative capacity decreased over time. Serum hs-CRP, plasma retinol, and β-carotene did not significantly change during the trial.In hypertensive patients, a high-energy meal did not lead to postprandial impairment of vascular endothelial function. Postprandial metabolic responses induced by the challenge, such as lipemia and insulinemia, were not attenuated by the concomitant ingestion of quercetin.This trial was registered at and as DRKS00000555.
Keywords: Quercetin; Blood pressure; Postprandial metabolism; Cardiovascular diseases; Endothelial function

Postprandial glucose and insulin levels in type 2 diabetes mellitus patients after consumption of ready-to-eat mixed meals by Yannis Manios; George Moschonis; Christina Mavrogianni; Konstantina Tsoutsoulopoulou; Stergios Kogkas; Christina-Paulina Lambrinou; Eirini Efstathopoulou (1359-1367).
To compare the effects of three ready-to-eat mixed meals, with a high fiber content and low glycemic index, on postprandial glycemic and insulinemic response in patients with Type 2 diabetes mellitus (T2DM).The current study followed a prospective, three-way, cross-over design. Twenty-four patients with T2DM consumed three ready-to-eat mixed meals, i.e., “wild greens pie” (meal 1), “chicken burgers with boiled vegetables” (meal 2) and “vegetable moussaka” (meal 3) and an oral glucose load, all providing 50 g of carbohydrates. Venous blood was collected at 0, 30, 60, 90 and 120 min postprandial. Statistical analyses included repeated measures analysis of variance and calculations of the area under the glucose and insulin curves (AUC) for each one of the test meals and the oral glucose load.Patients consuming each one of the three mixed meals showed better postprandial glycemic responses compared to the oral glucose load (P < 0.001). Furthermore, patients consuming meal 3 showed a better insulinemic response compared to the oral glucose load and meal 1, after 60 and 120 min postprandial, respectively (P < 0.05). In addition, the increase observed in HOMA-IR values from T0 to T120 was significantly lower for meal 3, compared to the oral glucose load (P < 0.001).The three ready-to-eat mixed meals examined in the present study were found to elicit significantly lower glycemic responses compared to the oral glucose load in diabetic patients. The mixed meals examined in the present study could be proposed as effective, palatable and practical solutions for diabetics for glucose control.
Keywords: Diabetes; Glycemic response; Insulinemic response; Mixed meals; Glycemic index

(−)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes by Isabel Cordero-Herrera; Xinpu Chen; Sonia Ramos; Sridevi Devaraj (1369-1373).
Diabetes is a pro-inflammatory state associated with increased monocyte activity. NF-κB is the master switch of inflammation and is activated during diabetes. (−)-Epicatechin (EC), the main cocoa flavonol, displays anti-inflammatory and anti-diabetic effects under high glucose conditions. Recently, it has been suggested that dietary polyphenols might modulate chromatin remodelling by epigenetic changes and regulate monocyte NF-κB activation and cytokine expression under diabetic conditions. The aim of the study was to test the potential anti-inflammatory role of EC via inducing posttranslational histone changes in the presence of a high glucose (HG) concentrations.Human monocytic cells (THP-1 cells) were pre-treated with EC (5 μM) and 4 h later exposed to 25 mM glucose (HG) for a total of 24 h. Control cells were grown under normoglycemic conditions (NG, 5.5 mM glucose). Acetyl CBP/p300, HDAC4, total histone 3 (HH3), H3K9ac, H3K4me2 and H3K9me2, and phosphorylated and total levels of p65-NF-κB were analysed by Western blot. Histone acetyltransferase (HAT) activity was measured in nuclear lysates, and TNF-α release was evaluated in culture media.EC incubation restored to control levels (NG) the changes induced by HG in p-p65/p65-NF-ĸB ratio, acetyl CBP/p300 values and HAT activity. Moreover, EC pre-treatment counteracted the increased acetylation of H3K9 and H3K4 dimethylation and attenuated the diminished H3K9 dimethylation triggered by HG. EC also significantly decreased HG-enhanced HDAC4 levels and TNF-α release, respectively.EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.
Keywords: Diabetes; Epicatechin; Epigenetics; Inflammation; Human monocytes THP-1 cells; Posttranslational histone modification