European Journal of Nutrition (v.52, #8)

Nutrition and neurodevelopment in children: focus on NUTRIMENTHE project by Tania Anjos; Signe Altmäe; Pauline Emmett; Henning Tiemeier; Ricardo Closa-Monasterolo; Verónica Luque; Sheila Wiseman; Miguel Pérez-García; Eva Lattka; Hans Demmelmair; Bernadette Egan; Niels Straub; Hania Szajewska; Jayne Evans; Claire Horton; Tomas Paus; Elizabeth Isaacs; Jan Willem van Klinken; Berthold Koletzko; Cristina Campoy (1825-1842).
There is growing evidence that early nutrition affects later cognitive performance. The idea that the diet of mothers, infants, and children could affect later mental performance has major implications for public health practice and policy development and for our understanding of human biology as well as for food product development, economic progress, and future wealth creation. To date, however, much of the evidence is from animal, retrospective studies and short-term nutritional intervention studies in humans. The positive effect of micronutrients on health, especially of pregnant women eating well to maximise their child’s cognitive and behavioural outcomes, is commonly acknowledged. The current evidence of an association between gestational nutrition and brain development in healthy children is more credible for folate, n-3 fatty acids, and iron. Recent findings highlight the fact that single-nutrient supplementation is less adequate than supplementation with more complex formulae. However, the optimal content of micronutrient supplementation and whether there is a long-term impact on child’s neurodevelopment needs to be investigated further. Moreover, it is also evident that future studies should take into account genetic heterogeneity when evaluating nutritional effects and also nutritional recommendations. The objective of the present review is to provide a background and update on the current knowledge linking nutrition to cognition and behaviour in children, and to show how the large collaborative European Project NUTRIMENTHE is working towards this aim.
Keywords: Nutrition; Children; Mental performance; Cognition; Brain assessment; Genetics

Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study by Emmanuel Barrat; Yassine Zaïr; Pascal Sirvent; Patrice Chauveau; Corinne Maudet; Béatrice Housez; Elodie Derbord; Jean-François Lescuyer; Jean-Marie Bard; Murielle Cazaubiel; Sébastien L. Peltier (1843-1852).
To determine the effect of 4 weeks of supplementation, then, withdrawal of a dietary supplement (DS) containing red yeast rice extract, policosanol and artichoke leaf extract at twice the recommended daily dose (6 tablets, 6-TAB) compared to the usual dose (3-TAB) or to a placebo (PLA), on blood lipid profiles and safety biomarkers.Forty-five healthy subjects (15 per group), with untreated hypercholesterolaemia, were included in this randomised, double-blind, placebo-controlled clinical trial.After 4 weeks of supplementation, LDL-C was significantly lower in 6-TAB (−0.21 g/l; 95 % CI −0.38 to −0.03 g/l; p = 0.0217) and 3-TAB (−0.25 g/l; 95 % CI −0.42 to −0.07 g/l; p = 0.0071) compared to PLA, although no difference in LDL-cholesterol was observed between the two groups, while no effect was seen on triacylglycerol and HDL-cholesterol. Four weeks after the end of supplementation, no difference in LDL-C was seen between the PLA group and the DS-treated groups. The muscle breakdown biomarkers, as well as biomarkers of liver and renal function, were altered by neither dose of the DS. Acute application of the DS on permeabilised skeletal muscle fibres of rats did not induce deleterious effects on mitochondrial function.Supplementation with twice the recommended dose of the DS was effective in reducing LDL-cholesterol and appeared safe, but according to the present results, no additional benefit could be achieved compared to the recommended dose.
Keywords: Red yeast rice; Policosanols; Artichoke leaf extract; Muscle breakdown; Withdrawal

Immunomodulatory effects of a probiotic drink containing Lactobacillus casei Shirota in healthy older volunteers by Honglin Dong; Ian Rowland; Linda V. Thomas; Parveen Yaqoob (1853-1863).
There is growing evidence that probiotics confer health benefits to the host by modulating immune function, especially in older people, where immunosenescence is a feature even of healthy ageing. The aim of this study was to investigate the effect of a probiotic drink containing Lactobacillus casei Shirota (LcS) on immune function in a healthy non-immunocompromised older population.Thirty healthy old volunteers were recruited into a randomized placebo-controlled, single-blind crossover study. The volunteers were supplemented with the probiotic drink containing 1.3 × 1010 CFU LcS or skimmed milk per day for 4 weeks, followed by 4 weeks of washout and were crossed over to the other treatment. Peripheral blood and saliva samples were collected at baseline and end of each treatment.Probiotic consumption was associated with a significant increase in natural killer (NK) cell activity relative to baseline and a significant decrease in the mean fluorescence intensity of CD25 expression in the resting T cells compared with placebo. Additionally, there was a trend towards an increased ratio of IL-10 to IL-12 relative to baseline after LcS intake.Consumption of a probiotic drink containing LcS improved NK cell activity and tended to produce a more anti-inflammatory cytokine profile in an older population.
Keywords: Cytokine; Immune function; Lactobacillus casei Shirota; Lymphocyte; Probiotic

Beneficial effects of omega-3 fatty acids on the consequences of a fructose diet are not mediated by PPAR delta or PGC1 alpha by Julie Karsenty; Jean-François Landrier; Delphine Rousseau-Ralliard; Vanessa Robbez-Masson; Alain Margotat; Paule Deprez; Paulette Lechêne; Alain Grynberg; Denis Lairon; Richard Planells; Marguerite Gastaldi (1865-1874).
To study, in high-fructose-fed rats, the effect of a dietary enrichment in omega-3 polyunsaturated fatty acids (n-3 PUFA) on the expression of genes involved in lipid metabolism and cardiovascular function.Twenty-eight male “Wistar Han” rats received for 8 weeks, either a standard chow food or an isocaloric 67 % fructose diet enriched or not in alpha-linolenic acid (ALA) or in docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) mix (DHA/EPA). After sacrifice, blood was withdrawn for biochemical analyses; heart, periepididymal adipose tissue and liver were collected and analyzed for the expression of 22 genes by real-time PCR.Fructose intake resulted in an increase in liver weight and triglyceride content, plasma triglyceride and cholesterol concentrations, although no difference in glucose and insulin. In the liver, lipogenesis was promoted as illustrated by an increase in stearoyl-CoA desaturase and fatty acid synthase (Fasn) together with a decrease in PPAR gamma, delta and PPAR gamma coactivator 1 alpha (PGC1 alpha) expression. In the heart, Fasn and PPAR delta expression were increased. The addition of ALA or DHA/EPA into the diet resulted in a protection against fructose effects except for the decreased expression of PPARs in the liver that was not counterbalanced by n-3 PUFA suggesting that n-3 PUFA and fructose act independently on the expression of PPARs and PGC1 alpha.In liver, but not in heart, the fructose-enriched diet induces an early tissue-specific reduction in PPAR gamma and delta expression, which is insensitive to n-3 PUFA intake and dissociated from lipogenesis.
Keywords: Wistar rats; Fructose intake; n-3 PUFA; PPAR delta; Liver; Gene expression

Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers by Gitte Ravn-Haren; Lars O. Dragsted; Tine Buch-Andersen; Eva N. Jensen; Runa I. Jensen; Mária Németh-Balogh; Brigita Paulovicsová; Anders Bergström; Andrea Wilcks; Tine R. Licht; Jarosław Markowski; Susanne Bügel (1875-1889).
Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the ‘5 or more a day’ campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors of CVD.Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood pressure in a group of 23 healthy volunteers.The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7 %), pomace (7.9 %) and cloudy juice (2.2 %) intake. On the other hand, LDL-cholesterol concentrations increased by 6.9 % with clear juice compared to whole apples and pomace. There was no effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, inflammation (hs-CRP), composition of the gut microbiota or markers of glucose metabolism (insulin, IGF1 and IGFBP3).Apples are rich in polyphenols and pectin, two potentially bioactive constituents; however, these constituents segregate differently during processing into juice products and clear juice is free of pectin and other cell wall components. We conclude that the fibre component is necessary for the cholesterol-lowering effect of apples in healthy humans and that clear apple juice may not be a suitable surrogate for the whole fruit in nutritional recommendations.
Keywords: Apples; Pomace; Clear juice; Blood lipids; CVD; ISAFRUIT

Maternal caffeine administration leads to adverse effects on adult mice offspring by Diana F. Serapiao-Moraes; Vanessa Souza-Mello; Marcia B. Aguila; Carlos A. Mandarim-de-Lacerda; Tatiane S. Faria (1891-1900).
This study aimed to evaluate the role of caffeine chronic administration during gestation of C57BL/6 mice on cardiac remodeling and the expression of components of the renin-angiotensin system (RAS) in male offspring as adults.Pregnant C57BL/6 female mice were divided into two groups (n = 10): Control group (C), dams were injected with the vehicle only (saline 0.9 % NaCl); Caffeine group (CF), dams received daily a subcutaneous injection of 20 mg/kg of caffeine/day (1 mg/mL saline). Pups had free access to standard chow since weaning to 3 months of age, when they were killed.CF group showed increased energy expenditure (+7 %) with consequent reduction in body mass (BM) gain (−18 %), increased blood pressure (+48 %), and higher heart rate (+10 %) than C group. The ratio between LV mass/BM was greater (+10 %), with bigger cardiomyocytes (+40 %), and reduced vascularization (−25 %) in CF group than in C group. In the LV, the expression of angiotensin-converting enzyme (+30 %), Angiotensin II (AngII) (+60 %), AngII receptor (ATR)-1 (+77 %) were higher, and the expression of ATR-2 was lower (−46 %; P < 0.05) in CF group than in C group. In the kidney, the expressions of renin (+128 %) and ATR-1 (+88 %) were higher in CF group than in C group.Chronic administration of caffeine to pregnant dams led to persistent activation of local RAS in the kidney and heart of the offspring, which, in turn, leads to high BP and adverse cardiac remodeling. These findings highlight the urge to encourage pregnant women to avoid food or medicines containing caffeine.
Keywords: Caffeine; Fetal programming; Energy expenditure; Cardiac hypertrophy; Renin-angiotensin system; Hypertension

To investigate the associations of dietary TAC from diet and supplements with serum antioxidant concentrations and serum C-reactive protein (CRP) and plasma total homocysteine (tHcy) in US adults.This was a cross-sectional study. Food consumption data, serum antioxidant levels, and serum CRP and Plasma tHcy concentrations of 4,391 US adults aged ≥19 years in the National Health and Nutrition Examination Survey 2001–2002 were analyzed. The USDA flavonoid and proanthocyanidin databases and dietary supplement data as well as antioxidant capacities of 43 antioxidants were also utilized.Serum CRP and plasma tHcy concentrations were higher in older adults, smokers, and those with lower non-leisure time physical activity levels (P < 0.05). Energy-adjusted daily total antioxidant capacity (TAC) from diet and supplements was positively associated with serum vitamin E and carotenoid concentrations (P < 0.05). Adjusted odds ratio (OR) for plasma tHcy >13 μmol/L significantly decreased across quartiles of TAC from diet and supplements (Q1 = 2.18 (1.56–2.77); Q2 = 1.30 (1.00–2.07); Q3 = 1.34 (0.84–2.28); Q4 = 1.00; P for linear trend <0.001). A negative trend across quartiles of TAC from diet and supplements was also observed in OR for serum CRP ≥3 mg/L (Q1 = 1.26 (0.97–1.70); Q2 = 1.21 (0.91–1.66); Q3 = 0.97 (0.80–1.24); Q4 = 1.00; P for linear trend <0.05).These findings indicated that dietary TAC provided an integrated conceptual tool in assessing serum antioxidants and investigating the associations between antioxidant intake and CVD risk. The implicated applicability of dietary TAC needs further validation in prospective cohort studies.
Keywords: Dietary total antioxidant capacity; Cardiovascular disease; C-reactive protein; Total homocysteine; Diet; Supplements

The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated.In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode.In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012).The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.
Keywords: Randomized; Placebo-controlled; Double-blind study; Insoluble yeast beta-glucan; Common cold; Immune system

Dietary, anthropometric, and lifestyle correlates of serum carotenoids in postmenopausal women by Agata Wawrzyniak; Jadwiga Hamułka; Emilie Friberg; Alicja Wolk (1919-1926).
Concentration of carotenoids in the serum is a biomarker of mainly vegetable and fruit consumption. However, the levels of carotenoids in humans may decline with age and can also depend on body fat, alcohol consumption, and cigarette smoking.Food intake and characteristics of 159 randomly chosen women aged 56–75 years were obtained by a self-administered questionnaire. Serum concentrations of carotenoids were determined by high-performance liquid chromatography. Estimation of fat mass was carried out by dual energy X-ray absorptiometry.The estimated total daily intake of carotenoids was 9.75 mg: α-carotene 10.6 %; β-carotene 35.6 %; lutein/zeaxanthin 27.1 %; β-cryptoxanthin 4.7 %; and lycopene 22.0 %. We observed statistically significant positive correlations between concentrations of serum carotenoids and their estimated intakes (r = 0.11 lycopene to 0.38 β-carotene) and fruit and vegetable intake (r = 0.15 lycopene to 0.30 β-carotene). Concentration of serum carotenoids positively correlated with education (r = 0.17 α-carotene to 0.29 lycopene) and alcohol intake (r = 0.02 α-carotene to r = 0.25 lycopene). Inverse correlations were with the age (r = −0.18 α-carotene to −0.42 lycopene) and fat mass (r = −0.15 lycopene to −0.29 α-, β-carotene).In this population of healthy postmenopausal women, serum concentrations of carotenoids declined with increasing age and body fat mass. The concentrations were increased among women with high vegetable and fruit consumption, moderate alcohol intake, and high level of education.
Keywords: Carotenoids; Serum; Diet; Correlations

Effect of Maillard reaction on biochemical properties of peanut 7S globulin (Ara h 1) and its interaction with a human colon cancer cell line (Caco-2) by Małgorzata Teodorowicz; Ewa Fiedorowicz; Henryk Kostyra; Harry Wichers; Elżbieta Kostyra (1927-1938).
The purpose of this study was to determine the influence of Maillard reaction (MR, glycation) on biochemical and biological properties of the major peanut allergen Ara h 1.Three different time/temperature conditions of treatment were applied (37, 60, and 145 °C). The extent of MR was assessed by SDS-PAGE, loss of free amino groups, fluorescence intensity, content of bound sugar and fructosamine. The Caco-2 model system was applied to study effects of hydrolysed and non-hydrolysed Ara h 1 on proliferation and interleukin-8 (IL-8) secretion from Caco-2 cells.We demonstrated significant differences in the biochemical properties of Ara h 1 glycated at different time/temperature conditions. Glycation of Ara h 1 at 37 °C was shown to cause least biochemical changes, not limiting pepsin hydrolysis. Loss of free amino groups, increase of fluorescence and brown colour of Ara h 1 glycated at 60 and 145 °C indicated advanced and final stages of MR. Non-treated Ara h 1 inhibited Caco-2 cell proliferation and stimulated IL-8 secretion. This effect was less pronounced for glycated Ara h 1. Incubation of Caco-2 cells with non-hydrolysed Ara h 1, glycated at the temperature of 37 and 60 °C, did not stimulate IL-8 secretion.Each applied time/temperature-treatment combination caused different biochemical changes of Ara h 1, underlining diversity of formed MRPs. MR, independently of temperature/time conditions, reduced the pro-inflammatory properties of native Ara h 1, reflected in stimulation of IL-8 secretion from intestinal epithelial cells.
Keywords: Ara h 1; Food allergy; Maillard reaction; Maillard reaction products (MRPs); IL-8; Caco-2 proliferation

Effects of a dietetic treatment in older, undernourished, community-dwelling individuals in primary care: a randomized controlled trial by Janneke Schilp; Hinke M. Kruizenga; Hanneke A. H. Wijnhoven; Jaap J. van Binsbergen; Marjolein Visser (1939-1948).
Undernutrition is a prevalent problem in older, community-dwelling individuals. Aim of this study was to determine the effects of a dietetic treatment in older, undernourished, community-dwelling individuals.A parallel randomized controlled trial was performed in 146 non-institutionalized, undernourished individuals aged ≥65 years in primary care. Participants were randomly assigned to the intervention (referral to and treatment by a trained dietitian) or control group (no referral). Body weight, physical performance, handgrip strength, energy intake, protein intake and fat-free mass were assessed at baseline, after 3 months and after 6 months.All randomized participants (n = 146) were included in the intention-to-treat generalized estimating equations analysis (72 in intervention and 74 in control group). No treatment effect was found on the primary outcomes body weight (β = 0.49 kg, 95 % CI: −0.15–1.12), physical performance (β = 0.15 points, 95 % CI: −0.33–0.64) and handgrip strength (β = 0.49 kg, 95 % CI: −0.62–1.60). Furthermore, no treatment effect was found for the secondary outcomes. Predefined subgroup analyses showed a treatment effect on body weight in physically active participants (β = 1.25 kg, 95 % CI: 0.70–2.11) and not in inactive participants (β = −0.20 kg, 95 % CI: −1.16–0.75).After 6 months, a dietetic treatment by trained dietitians does not lead to increases in body weight and physical functioning in older, undernourished, community-dwelling individuals.
Keywords: Undernutrition; Older individuals; Primary care; Dietetic treatment

Sulforaphane inhibits growth of phenotypically different breast cancer cells by Anna Pawlik; Aleksandra Wiczk; Angelika Kaczyńska; Jędrzej Antosiewicz; Anna Herman-Antosiewicz (1949-1958).
Cancer development and resistance to chemotherapy correlates with aberrant activity of mitogenic pathways. In breast cancers, pro-survival PI3K-AktmTOR-S6K1 signaling pathway is often hyperactive due to overexpression of genes coding for growth factors or estrogen receptors, constitutive activation of PI3K or Akt and loss of PTEN, a negative regulator of the pathway. Since epidemiologic as well as rodent tumor studies indicate that sulforaphane (SFN), a constituent of many edible cruciferous vegetables, might be a potent inhibitor of mammary carcinogenesis, we analyzed the response of four breast cancer cell lines representing different abnormalities in ErbB2/ER-PI3K-AktmTOR-S6K1 signaling pathway to this compound.Four different breast cancer cell lines were used: MDA MB 231, MCF-7, SKBR-3 and MDA MB 468. Cell viability and ultrastructure, protein synthesis, autophagy induction and phosphorylation status of Akt and S6K1 kinases upon SFN treatment were determined.We observed that all four cell lines are similarly sensitive to SFN. SFN decreased phosphorylation of Akt and S6K1 kinases and at higher concentrations induced autophagy in all studied cell lines. Moreover, global protein synthesis was inhibited by SFN in investigated cell lines in a dose-dependent manner.These results indicate that SFN is a potent inhibitor of the viability of breast cancer cells representing different activity of the ErbB2/ER-PI3K-AktmTOR-S6K1 pro-survival pathway and suggest that it targets downstream elements of the pathway.
Keywords: Breast cancer; Sulforaphane; PI3K-AktmTOR-S6K1 pathway; Autophagy

Erratum to: Sulforaphane inhibits growth of phenotypically different breast cancer cells by Anna Pawlik; Aleksandra Wiczk; Angelika Kaczyńska; Jędrzej Antosiewicz; Anna Herman-Antosiewicz (1959-1959).