European Journal of Nutrition (v.47, #3)

Nutrition and children’s cognition: research methods and findings by Maureen M. Black; Bonnie Kaplan; Joachim Westenhöfer (1-2).

Introduction (3-3).

Although studying the effects of diet on cognitive function in children is of great interest to nutritionists, many have not received the formal training in the principles and practice of assessment necessary to properly evaluate research studies or to design and conduct research themselves. This paper is aimed at such an audience and assumes little prior knowledge of the field. A short description of neural development in childhood is followed by a discussion of important principles of assessment. A level of assessment approach is used to present a selection of widely used cognitive tests organized by cognitive domain and age group. Practical information about the tests is presented in tabular form and a list of useful websites is included.
Keywords: cognition; children; psychological assessment; nutrition

The rapid growth of the brain and its high metabolic rate suggests that it is reasonable to consider whether their diet may influence the cognitive development of children. To date although there are few nutritional recommendations that can be made with confidence, there is a growing body of evidence that diet can influence the development and functioning of the brain. Several lines of evidence support the view that the diet of the mother during pregnancy, and the diet of the infant in the perinatal period, have long-term consequences. The provision of fatty acids has been the most studied aspect of nutrition, although the evidence is lacking that supplementation has long-term benefits. There is increasing evidence that the missing of breakfast has negative consequences late in the morning and a working hypothesis is that meals of a low rather than high glycemic load are beneficial. The aim is to introduce a range of topics to those for whom this area is of potential interest. Where appropriate the main themes and conclusions are summarized and attention is drawn to review articles that allow those interested to go further.
Keywords: breakfast; brain development; food intolerance; malnutrition

It is widely accepted that the rapid rate of growth of the brain during the last third of gestation and the early postnatal stage makes it vulnerable to an inadequate diet, although brain development continues into adulthood and micronutrient status can influence functioning beyond infancy. A deficiency of various micro-nutrients in developing countries has been found to have long-term implication for cognitive development. Vitamin A plays a critical role in visual perception and a deficiency is the leading cause of childhood blindness. A lack of iodine during a critical period in brain development is associated with reduced intellectual ability. Iron shortage is a widespread problem in the developing world but also in industrialized countries. There is evidence that iron deficiency in early life adversely effects brain development. In addition in industrialized countries a role for folate in the prevention of neural tube defects is well established and in a few individuals impaired cognitive functioning is associated with the inadequate provision of vitamin B12. The controversial suggestions that sub-clinical deficiencies of micronutrients may in industrialized societies influence anti-social behavior and intelligence are also discussed.
Keywords: childhood; cognition; micro-nutrient; behavior

Chemoprevention by white currant is mediated by the reduction of nuclear β-catenin and NF-κB levels in Min mice adenomas by Johanna Rajakangas; Marjo Misikangas; Essi Päivärinta; Marja Mutanen (115-122).
Berries are a good natural source of phenolic compounds and many berries or their compounds have been shown to be chemopreventive. White currant is an interesting berry, as it contains low levels of dominant berry phenolics such as ellagic acid, anthocyanins and other flavonoids.To study if white currant is chemopreventive in an experimental model for intestinal tumorigenesis and further study the effects on β-catenin and NF-κB signaling pathways.Multiple intestinal neoplasia (Min) mice were fed an AIN-93G based control diet or a diet containing 10% freeze dried white currant (Ribes x pallidum) for 10 weeks. Cell signaling parameters were analysed from intestinal adenomas and surrounding mucosa by Western blotting and immunohistochemistry.The white currant diet reduced the number of adenomas from 81 (min–max 47–114) to 51 (36–84) in the total small intestine of Min mice (P < 0.02). Most of the adenomas develop in the distal part of the small intestine, and in this area white currant reduced the number from 49 to 29.5 (P < 0.01) and also the size of the adenomas from 0.88 mm to 0.70 mm (P < 0.02). In the colon white currant increased the number of adenomas (0.3 ± 0.6 vs. 0.8 ± 0.6, mean ± SD, P < 0.05), but did not affect the size. White currant reduced nuclear β-catenin and NF-κB protein levels in the adenomas (P < 0.05 and P < 0.02, respectively). They were correlated with the size of adenomas (P < 0.01).This study shows that white currant is effective in preventing cancer initiation and progression in the Min mouse. Whether the positive effects are due to its special phenolic composition needs to be studied in more detail.
Keywords: white currant; colon cancer; Min mouse; β-catenin; NF-κB

Dietary lipid intake influences the level of cholesterol bound to haemoglobin in human erythrocytes by Milan Nikolic; Danijela Ristic Medic; Dragana Stanic; Marija Postic; Aleksandra Arsic; Vesna Niketic (123-130).
Blood cholesterol levels are affected by diet and in particular by the type of fat intake. We originally showed that a significant but variable amount of cholesterol is firmly bound to haemoglobin (Hb) yielding the Hb-lipid adduct (Hb-Ch) in erythrocytes isolated from normo-lipidemic males.To establish whether dietary lipids affect the level of Hb-Ch in human erythrocytes.Seventy-four healthy free-living adults were separated according to their serum cholesterol levels into two groups: normo-cholesterolemic (LDL cholesterol <3.4 mmol/l and total cholesterol <5.2 mmol/l) (NC) and hyper-cholesterolemic (LDL cholesterol ≥3.4 mmol/l) (HC). Habitual dietary information was used to classify subjects in both study groups into sub-groups of low-fat (≤30% total energy as fat) and high-fat consumers (>30% total energy as fat). The NC low-fat consumers were placed on a high-lipid (high-fat and high-cholesterol) diet whereas the HC subjects with high-fat intake were assigned to a low-lipid (low-fat and low-cholesterol) diet. Both types of dietary intervention were allowed to continue for 6 weeks. The main variable under scrutiny was the Hb-Ch concentration.In both study groups low-fat intake subjects had low levels of Hb-Ch (approx. 0.35 mmol/l RBC) compared with high-fat intake subjects (approx. 0.60 mmol/l RBC), and serum cholesterol was not correlated with Hb-Ch. The two dietary interventions produced substantial changes in the Hb-Ch level that paralleled variation in the serum cholesterol concentration. A high-lipid diet (35% fat, 15% saturated; 580 mg cholesterol) increased Hb-Ch (by approximately 47%, P < 0.001) in subjects with low Hb-Ch at onset, whereas a low-lipid diet (28% fat, 9% saturated; 280 mg cholesterol) decreased Hb-Ch (by approximately 40%, P < 0.001) in subjects with high Hb-Ch at onset.High consumption of dietary lipids, including saturated fat and cholesterol, has an important influence on the level of Hb-Ch in human erythrocytes.
Keywords: dietary lipids; cholesterol; saturated fat; haemoglobin; human erythrocytes

Supplement use and mortality: the SENECA study by Anna Brzozowska; Joanna Kaluza PhD; Kim T. B. Knoops PhD; Lisette C. P. G. M. de Groot (131-137).
It is hypothesis that in relatively healthy older people supplement usage can be consider as healthy life style habit and as such can positively influence longevity.To determine whether supplement use was associated with all-cause mortality in the participants of the SENECA study.Baseline measurements were carried out in 1988/1989 among 75 to 80-year-old people living in 15 European small towns. All-cause mortality was followed up to April 30, 1999. Data from 920 men and 980 women who were ischemic heart diseases-, stroke- and cancer-free at baseline were included. The multivariate adjusted (for sex, age, years of education, physical activity, BMI, chronic diseases, Mediterranean Diet Score, alcohol use and the place of living) hazard ratio (HRs) and 95% confidence intervals (CIs) of mortality by use of any type of nutrient supplement and by particular nutrient supplement use were estimated by Cox proportional hazards regression models.At baseline, 13% of participants used nutritional supplements, 19% of subjects were smokers. During 10 years of follow-up 445 men and 252 women died. Among non-smokers no significant associations between total supplement use and particular nutrient supplement use were observed. Among smokers use of any type of supplements (Multivariate HR: 1.52; 95%CI: 1.02–2.28), use of vitamin B1 (Multivariate HR: 1.57; 95%CI: 1.00–2.48) and vitamin B2 supplements (Multivariate HR: 1.60; 95%CI: 1.00–2.56) were associated with a significantly higher risk of all-cause mortality. The similar tendencies were observed among vitamin B6 and vitamin C supplement users who were smokers.Among smokers, participants of the SENECA study, supplement use increased all-cause mortality risk.
Keywords: elderly; Europe; supplement use; mortality; smoking

Soy intake is related to a lower body mass index in adult women by Gertraud Maskarinec MD, PhD; Alison G. Aylward BA; Eva Erber MS; Yumie Takata MS; Laurence N. Kolonel MD, PhD (138-144).
Experimental and epidemiologic studies suggest that soy may promote weight loss.The goal of this study was to examine the relation of soy intake with body weight over the lifespan of women with Caucasian, Japanese, and Native Hawaiian ancestry.We assessed the relation between lifetime soy consumption and body mass index (BMI) among 1,418 women in Hawaii. All subjects reported anthropometric measures, regular diet, and soy intake throughout life. The lifetime soy questionnaire was completed again by a subset of 356 women 5 years after study entry and the κ values indicated moderate agreement. We regressed soy intake on BMI at study entry and at age 21 while controlling for confounding variables, computed least square means, and performed trend tests.Higher soy consumption in adulthood was related to a lower BMI (P = 0.02). This association was only significant for Caucasian women and for postmenopausal subjects. The women in the highest category also experienced a smaller annual weight change since age 21 (by 0.05 kg/year) than the low soy intake group (P = 0.02). We observed no association between early life soy intake and BMI. High vegetable consumption was significantly associated with a higher soy intake among Caucasian women.In this study, women consuming more soy during adulthood had a lower BMI, but the relation was primarily observed for Caucasian and postmenopausal subjects. This indicates that the association may be due to other nutritional factors and behaviors common in women with high soy intake.
Keywords: soy; body mass index; obesity; ethnicity; early life nutrition

The effect of maternal T1DM on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidyethanolamine in infants during early life by Christiane Winkler; Sandra Hummel; Maren Pflüger; Anette-G. Ziegler; Julia Geppert; Hans Demmelmair; Berthold Koletzko (145-152).
The risk for type 1 diabetes (T1DM) in children of mothers with T1DM is different to that in children of fathers with T1DM. Fatty acid (FA) intake, in particular EPA and DHA, has been associated with T1DM risk and has been suggested to be inadequate in infants of diabetic mothers. We asked, therefore, whether EPA and DHA FA nutritional status in offspring of mothers with T1DM could contribute to their reduced T1DM riskBABYDIET follows children with increased genetic and familial risk for T1DM from birth to age 3 years. FA nutritional state was assessed by determining the erythrocyte membrane phosphatidylethanolamine (PE) and phosphatidylcholine (PC) composition in children of T1DM mothers and children of T1DM fathers or with T1DM siblings participating in the BABYDIET study. Samples for determination of erythrocyte membrane FA composition were collected at ages 3 and 12 months in 48 and 49 infants, respectively. FA measurements were adjusted for breastfeeding duration, FA supplementation, and gluten exposure.3-months-old children of T1DM mothers and T1DM fathers/sibs had similar levels of PC DHA and EPA (DHA 1.53 ± 0.23 vs. 1.65 ± 0.11 wt.%; EPA 0.15 ± 0.02 vs. 0.21 ± 0.03 wt.%) and PE DHA and EPA (DHA 7.54 ± 0.37 vs. 7.92 ± 0.38 wt.%; EPA 0.53 ± 0.06 vs. 0.61 ± 0.04 wt.%). No differences were also observed after stratification for breastfeeding. At age 12 months, a minor reduction of PE DHA was observed in children of T1DM mothers. Expected higher levels for DHA and EPA in fully breastfed children and in children of mothers taking fish oil supplementation were observed at 3 months in all children. Other differences included increased levels of the major saturated FA 16:0 in 3-months-old infants from T1DM mothers (PC 35.45 ± 0.35 vs. 33.89 ± 0.26 wt.%, mean ± SEM, P corr = 0.005; PE 16.13 ± 0.39 vs. 14.93 ± 0.24 wt.%, P corr = 0.05).Although FA status was not identical in children from T1DM mothers and from T1DM fathers, maternal T1DM was not associated with changes in offspring’s EPA and DHA incorporation into erythrocyte membrane.
Keywords: type 1 diabetes; erythrocyte membrane; DHA and EPA; breastfeeding; fish oil supplementation

Low n-6:n-3 fatty acid ratio, with fish- or flaxseed oil, in a high fat diet improves plasma lipids and beneficially alters tissue fatty acid composition in mice by Natalie D. Riediger; Rgia Othman; Evelyn Fitz; Grant N. Pierce; Miyoung Suh; Dr. Mohammed H. Moghadasian (153-160).
Health benefits from low n-6:n-3 fatty acid (FA) ratio on cardiovascular risk have been shown. However, the impact of the source of n-3 FAs has not been fully investigated.Our purpose was to investigate cardiovascular benefits of oils with a low ratio of n-6:n-3 FAs, but different sources of n-3 FAs in C57BL/6 mice.Twenty-one mice were divided into 3 groups (n = 7) and fed a diet supplemented with either a fish or flaxseed oil-based ‘designer oils’ with an approximate n-6:n-3 FA ratio of 2/1 or with a safflower-oil-based diet with a ratio of 25/1, for 16 weeks. Plasma lipids and fatty acid profile of the liver tissue were characterized.Compared to baseline, plasma triacylglycerol levels declined (>50%) in all groups by week 4. Plasma cholesterol levels were reduced in both fish and flax groups by 27% and 36%, respectively, as compared to controls at endpoint. The levels of EPA and DHA in liver phospholipids were significantly increased in both fish and flax groups as compared to the control group, with more profound increases in the fish group. Arachidonic acid levels were similarly decreased in the liver tissues from both fish and flax groups as compared to controls.Our data suggest that health benefits may be achieved by lowering dietary n-6:n-3 FA even in a high fat diet medium.
Keywords: eicosapentaenoic acid; α-linolenic acid; docosahexaenoic acid; cardiovascular; flaxseed oil; fish oil; mice

Obesity-related promotion of aberrant crypt foci in DMH-treated obese Zucker rats correlates with dyslipidemia rather than hyperinsulinemia by Tatiana C. L. Koch; Karlis Briviba; Bernhard Watzl; Achim Bub; Stephan W. Barth (161-170).
Obesity and energy restriction modulate the development of precancerous aberrant crypt foci (ACF) in animal models of colon cancer.Investigation of the major obesity-associated determinants for ACF-development and underlying mechanisms leading to ACF-modulation, such as changes in DNA damage or colonocytes hyperproliferation.Lean and obese Zucker rats fed ad libitum (a.l.) or obese pair fed (p.f.) were induced with 1,2-dimethylhydrazine (DMH) for colon cancer. Multiple regression analyses were performed to identify major metabolic factors correlated with ACF number and size (aberrant crypts/ACF). DNA damage is analyzed by the comet-assay, epithelial proliferation by immunohistochemistry.Aberrant crypt foci number was significantly elevated in Zucker obese a.l. (205.7 ± 65.4 vs. lean 9.5 ± 6.3, P < 0.05) and is reduced by pair feeding in Zucker obese rats (81.4 ± 28.5 vs. obese a.l., P < 0.05). Compared to lean the ACF size was higher in Zucker obese a.l. (2.1 ± 0.3 vs. lean 1.3 ± 0.2., P < 0.05) but is not reduced by pair feeding (1.7 ± 0.2; P > 0.05). While ACF number and size were modulated by genotype and/or pair feeding the DMH-induced DNA damage and hyperproliferation in colonocytes did not differ significantly between groups. Regression analysis showed that plasma parameters associated with lipid-metabolism (triglycerides, cholesterol, malondialdehyde) significantly correlated with the ACF number and size while parameters linked to carbohydrate-metabolism (glucose, insulin) were weaker determinants.Obesity or pair feeding-associated modulation of ACF correlate with parameters related to lipid-metabolism but is not accompanied by changes in DNA damage and proliferation.
Keywords: colon cancer; energy restriction; malondialdehyde; proliferation; DNA damage