European Journal of Nutrition (v.47, #1)

There is increasing evidence that higher intakes of carotenoids could protect against oxidative and light damage in premature infants and may promote other health benefits in both mothers during pregnancy and lactation and in newborn infants.To develop and validate a brief quantitative food frequency questionnaire (FFQ) aimed at assessing lutein and zeaxanthin intake in women.In this cross-sectional study, estimates of lutein and zeaxanthin intake from the FFQ were compared with a 7-day dietary record and with plasma concentrations of these carotenoids. This primary care study was conducted in Pavia, Italy. Subjects were all female volunteers, aged 20–25 years (mean age 22.7 ± 2.1 years), university students. Of the 110 women initially recruited, 87 completed diet questionnaires and donated a blood sample. Dietary intake was assessed by the FFQ by interview and 7-day dietary records chosen as a reference standard, using photographic estimations of portion sizes. Plasma concentrations of lutein and zeaxanthin were measured by HPLC. Pearson’s correlation coefficient and Bland Altman Regression analysis were used.Mean dietary lutein and zeaxanthin intakes were 1,107 ± 113 µg/day from the FFQ questionnaire and 1,083 ± 116 µg/day from the 7 day dietary records. The mean difference in intake assessed by the two methods (−24.5 ± 38.3 µg/day) did not differ significantly from zero. Dietary intake of lutein and zeaxanthin measured with the FFQ and plasma nutrient concentration among this sample were significantly correlated (r = 0.76, P < 0.0001). Mean plasma lutein and zeaxanthin concentrations were 0.33 ± 0.09 µmol/l.This FFQ could be used to assess lutein and zeaxanthin intake in adult women.
Keywords: FFQ; lutein (L) and zeaxanthin (Z) intake; plasma lutein (L); zeaxanthin (Z)

How we will produce the evidence-based EURRECA toolkit to support nutrition and food policy by Margaret Ashwell; Janet P. Lambert; Martine S. Alles; Francesco Branca; Luca Bucchini; Anna Brzozowska; Lisette C. P. G. M. de Groot; Rosalie A. M. Dhonukshe-Rutten; Johanna T. Dwyer; Sue Fairweather-Tait; Berthold Koletzko; Mirjana Pavlovic; Monique M. Raats; Lluis Serra-Majem; Rhonda Smith; Ben van Ommen; Pieter van ’t Veer; Julia von Rosen; Loek T. J. Pijls (2-16).
There is considerable variation in the recommended micronutrient intakes used by countries within Europe, partly due to different methodologies and concepts used to determine requirements and different approaches used to express the recommendations. As populations become more mobile and multi-national, and more traditional foods become available internationally, harmonised recommendations based on up to date science are needed. This was recognised by the European Commission’s (EC) Directorate-General (DG) Research in their 2005 call for proposals for a Network of Excellence (NoE) on ’nutrient status and requirements of specific vulnerable population groups’. EURopean micronutrient RECommendations Aligned (EURRECA), which has 34 partners representing 17 European countries, started on its 5-year EC-funded programme in January 2007. The programme of work was developed over 2 years prior to submitting an application to the EC. The Network’s first Integrating Meeting (IM) held in Lisbon in April 2007, and subsequent consultations, has allowed further refinement of the programme.This paper presents the rationale for the EURRECA Network’s roadmap, which starts by establishing the status quo for devising micronutrient recommendations. The Network has the opportunity to identify previous barriers and then explore ’evidence-based’ solutions that have not been available before to the traditional panels of experts. The network aims to produce the EURRECA ’toolkit’ to help address and, in some cases, overcome these barriers so that it can be used by those developing recommendations.The status quo has been largely determined by two recent initiatives; the Dietary Reference Intake (DRI) reports from the USA and Canada and suggestions for approaches to international harmonisation of nutrient-based dietary standards from the United Nations University (UNU). In Europe, the European Food Safety Authority (EFSA) has been asked by the EC’s Directorate-General for Health and Consumer Protection to produce values for micronutrient recommendations. Therefore, EURRECA will draw on the uniqueness of its consortium to produce the sustainable EURRECA toolkit, which will help make such a task more effective and efficient. Part of this uniqueness is the involvement in EURRECA of small and medium-sized enterprises (SMEs), consumer organisations, nutrition societies and other stakeholders as well as many scientific experts. The EURRECA toolkit will contain harmonised best practice guidance for a more robust science base for setting micronutrient recommendations. Hence, in the future, the evidence base for deriving nutrient recommendations will have greater breadth and depth and will be more transparent.The EURRECA Network will contribute to the broader field of food and nutrition policy by encouraging and enabling the alignment of nutrient recommendations. It will do this through the development of a scientific toolkit by its partners and other stakeholders across Europe. This will facilitate and improve the formulation of micronutrient recommendations, based on transparently evaluated and quantified scientific evidence. The Network aims to be sustainable beyond its EC funding period.
Keywords: EURRECA; Network of Excellence; micronutrients; nutrient recommendations; nutrient requirements; food policy; nutrition policy; health; EURRECA toolkit; harmonisation

Effects of black and green tea consumption on blood glucose levels in non-obese elderly men and women from Mediterranean Islands (MEDIS epidemiological study) by Evangelos Polychronopoulos MD, PhD; Akis Zeimbekis MD; Christina-Maria Kastorini RD; Natassa Papairakleous RD, MSc; Ioanna Vlachou MD; Vassiliki Bountziouka RD, MSc; Demosthenes B. Panagiotakos PhD (10-16).
Obesity and diabetes are metabolic disorders that affect a large amount of the elderly population and are related to increased cardiovascular risk. Tea intake has been associated with lower risk of mortality and morbidity in some, but not all studies. We evaluated the association between tea intake, blood glucose levels, in a sample of elderly adults.During 2005–2006, 300 men and women from Cyprus, 142 from Mitilini and 100 from Samothraki islands (aged 65–100 years) were enrolled. Dietary habits (including tea consumption) were assessed through a food frequency questionnaire. Among various factors, fasting blood glucose and body mass index (BMI) were measured.Fifty-four percent of the participants reported that they consume tea at least once a week (mean intake 1.6 ± 1.1 cup/day). A significant interaction was observed between tea intake, obesity status on glucose levels (P < 0.001). After adjusting for various confounders, tea intake was associated with lower blood glucose levels in non-obese (P for trend <0.001), but not in obese people (P = 0.24). Multiple logistic regression analysis revealed that moderate tea consumption (1–2 cups/day) was associated with 88% (95% CI 76–98%) lower odds of having diabetes among non-obese participants, irrespective of age, sex, smoking, physical activity status, dietary habits and other clinical characteristics.Tea consumption is associated with reduced levels of fasting blood glucose only among non-obese elderly people.
Keywords: diabetes; obesity; cardiovascular risk factors; tea; elderly

Minimising the population risk of micronutrient deficiency and over-consumption: a new approach using selenium as an example by Andrew G. Renwick; Lars O. Dragsted; Reg J. Fletcher; Albert Flynn; John M. Scott; Sandra Tuijtelaars MSc; T. Wildemann (17-25).
At the present time the recommended daily intake or allowance (RDA) and the safe upper level (UL) of intake of micronutrients are given as single values. The recommended daily intake is considered to cover the requirements of 97.5% of the population while the safe upper level is a value for the whole population. These values provide only limited guidance to risk managers.A method has been developed recently which models the relationships between intake and risks of either deficiency or excess using an observed incidence for each effect and population distribution characteristics. Using this model it is possible to formulate advice to risk managers on the incidence (prevalence) of adverse effects, due to either deficiency or excess, at different levels of intake. Application of the model to the data used to derive the RDA and UL for selenium shows that it can predict the impact of changes in nutrient intake on the balance between benefit (absence of deficiency) and risk (development of toxicity).Application of the model has illustrated the utility of this approach, but highlighted the need for a comprehensive evaluation of the data and a critical appraisal of the validity of the relationships that are analyzed. In addition, the derived incidences will usually relate to effects with different biological or health impacts, so that the final balance between benefit and risk should be developed by a dialogue between the risk assessor and the risk manager.
Keywords: risk-benefit analysis; micronutrients; selenium; recommended daily allowance; upper intake level; population-based analysis

Current micronutrient recommendations in Europe: towards understanding their differences and similarities by Esmée L. Doets; Liesbeth S. de Wit; Rosalie A. M. Dhonukshe-Rutten; Adriënne E. J. M. Cavelaars; Monique M. Raats; Lada Timotijevic; Anna Brzozowska; Trudy M. A. Wijnhoven; Mirjana Pavlovic; Torunn Holm Totland; Lene F. Andersen; Jiri Ruprich; Loek T. J. Pijls; Margaret Ashwell; Janet P. Lambert; Pieter van ’t Veer; Lisette C. P. G. M. de Groot (17-40).
Nowadays most countries in Europe have established their own nutrient recommendations to assess the adequacy of dietary intakes and to plan desirable dietary intakes. As yet there is no standard approach for deriving nutrient recommendations, they may vary from country to country. This results in different national recommendations causing confusion for policy-makers, health professionals, industry, and consumers within Europe. EURRECA (EURopean micronutrient RECommendations Aligned) is a network of excellence funded by the European Commission (EC), and established to identify and address the problem of differences between countries in micronutrient recommendations. The objective of this paper is to give an overview of the available micronutrient recommendations in Europe, and to provide information on their origin, concepts and definitions. Furthermore this paper aims to illustrate the diversity in European recommendations on vitamin A and vitamin D, and to explore differences and commonalities in approaches that could possibly explain variations observed.A questionnaire was developed to get information on the process of establishing micronutrient recommendations. These questionnaires were sent to key informants in the field of micronutrient recommendations to cover all European countries/regions. Also the latest reports on nutrient recommendations in Europe were collected. Standardisation procedures were defined to enable comparison of the recommendations. Recommendations for vitamin A and vitamin D were compared per sex at the ages 3, 9 months and 5, 10, 15, 25, 50 and 70 years. Information extracted from the questionnaires and reports was compared focusing on: (1) The concept of recommendation (recommended daily allowance (RDA), adequate intake (AI) or acceptable range), (2) The year of publication of the report (proxy for available evidence), (3) Population groups defined, (4) Other methodological issues such as selected criteria of adequacy, the type of evidence used, and assumptions made.Twenty-two countries, the World Health Organization (WHO)/the Food and Agriculture Organization of the United Nations (FAO) and the EC have their own reports on nutrient recommendations. Thirteen countries based their micronutrient recommendations on those from other countries or organisations. Five countries, WHO/FAO and the EC defined their own recommendations. The DACH-countries (Germany, Austria and Switzerland) as well as the Nordic countries (Norway, Sweden, Finland, Denmark and Iceland) cooperated in setting recommendations. Greece and Portugal use the EC and the WHO/FAO recommendations, respectively and Slovenia adopted the recommendations from the DACH-countries. Rather than by concepts, definitions, and defined population groups, variability appears to emerge from differences in criteria for adequacy, assumptions made and type of evidence used to establish micronutrient recommendations.The large variation in current micronutrient recommendations for population groups as illustrated for vitamin A and vitamin D strengthens the need for guidance on setting evidence based, up-to-date European recommendations. Differences in endpoints, type of evidence used to set recommendations, experts’ opinions and assumptions are all likely to contribute to the identified variation. So far, background information was not sufficient transparent to disentangle the relative contribution of these different aspects.EURRECA has an excellent opportunity to develop tools to improve transparency on the approaches used in setting micronutrient recommendations, including the selection of criteria for adequacy, weighing of evidence, and interpretation of data.
Keywords: micronutrients; recommendations; nutrient requirements; EURRECA

Methylmalonic acid values in healthy Dutch children by Marije Hogeveen; Ingrid van Beynum; Arno van Rooij; Leo Kluijtmans; Martin den Heijer; Henk Blom (26-31).
Plasma methylmalonic acid (MMA) is a specific marker for functional cobalamin deficiency. This deficiency can give rise to non-specific but serious symptoms in childhood such as developmental delay, convulsions and failure to thrive and may even lead to irreversible neurological damage.To analyse plasma MMA concentrations in Dutch children and to evaluate possible factors influencing its concentration.A number of 186 Dutch children aged 0–19 years were analysed cross-sectionally. Blood was collected to measure MMA, total homocysteine (tHcy), cobalamin (Cbl) and serum creatinine concentrations. In addition, information about medical history, age and sex was recorded.The geometric mean (GM) plasma MMA concentration was 0.17 µmol/l (95% CI 0.07–0.42) and the GM tHcy was 6.6 µmol/l (95% CI 3.1–13.9). There is a slight positive correlation between plasma MMA and age in children >1 year (r = 0.211, P < 0.05). Plasma MMA concentrations were significantly higher in children with low Cbl concentrations. No significant difference in MMA, Cbl, tHcy or creatinine concentrations between sexes could be observed. Regression analysis showed that Cbl was the strongest determinant of plasma MMA (regression coefficient −0.414, P < 0.05). The association between MMA and Cbl is stronger at increasing age (P for trend 0.045).Plasma Cbl is the main determinant of MMA in this group of Dutch children. The strength of the association increased with increasing age.
Keywords: methylmalonic acid; cobalamin; children

Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects by Nuria Plana; Catherine Nicolle; Raimon Ferre; Jordi Camps; Rosa Cos; Jesus Villoria; Dr. Luis Masana (32-39).
The number of hypercholesterolemic individuals who do not meet their cholesterol recommended targets is inappropriately high. The use of plant sterol-enriched foods could help in this clinical setting.To evaluate the efficacy and side effects of plant sterol-enriched fermented milk in reducing LDL-cholesterol and increasing the number of patients who attain their therapeutic targets.This was a multicentre, randomised, double-blind, placebo-controlled, parallel clinical trial. Eighty-three hypercholesterolemic patients that were not at therapeutic goals were studied. The patients received one 100 ml serving of either plain (control) low-fat or phytosterol enriched (1.6 g of free sterol equivalents) drinkable yogurt per day along with the main meal for 42 days. The principal variables were variation on LDL cholesterol (LDL-C) concentration and the number of patients achieving therapeutic goals after intervention.Patients on phytosterols attained an average LDL-C reduction of more than 10% (12.2% after 3 weeks; 10.6% after 6 weeks) (P = 0.001; 95% CI: 4.03–19.00) regardless of statin therapy compared to the control group. About 50% of the subjects on phytosterols, as compared to 20% of controls, attained their LDL-C target values (<3.3 or <2.6 mmol/l for primary and secondary prevention, respectively) at the end of the study (P < 0.001). HDL-cholesterol (HDL-C) did not change and triglycerides (TG) were decreased by 14% (P < 0.018). The plasma sterols/total cholesterol ratio increased.Plant sterol-enriched fermented milk significantly reduced LDL-C and increased the number of moderately hypercholesterolemic patients achieving therapeutic targets.
Keywords: LDL-cholesterol; coronary disease; plant sterols; fermented milk

Influence of dietary iodine on the iodine content of pork and the distribution of the trace element in the body by Katrin Franke; Friedrich Schöne; Andreas Berk; Matthias Leiterer; Gerhard Flachowsky (40-46).
Millions of people worldwide still suffer from iodine deficiency disorders. Besides salt iodination, iodine is added to animal feed to concentrate it in food of animal origin (milk, eggs, meat). Otherwise possible adverse effects of high supplementation should be avoided.The objective of the study was to evaluate the iodine content of pork at various feed iodine concentrations to estimate its contribution to human iodine supply. Furthermore the handling of low and high iodine dosages by the organism should be investigated using the pig as a model for the human.Seventy pigs (live weight period 27–115 kg), divided into five groups, were fed diets supplemented with 0 (group 1), 0.5 (group 2), 1 (group 3), 2 (group 4) and 5 (group 5) mg iodine per kg diet. Iodine was determined in the thyroid and in the fractions innards/blood, bones and muscle/fat of four pigs of each group by ICP-MS.Rising iodine supplementation of feed significantly increased (P < 0.05) the iodine content of the muscle/fat fraction [3.9 (group 1), 6.0 (group 2), 8.5 (group 3), 10.8 (group 4) and 17.1 (group 5) µg I/kg]. Carry over (of supplemented iodine) into muscle/fat varied between 0.10 and 0.24%. The highest tested iodine dosage (5 mg I/kg diet) caused a 3.6-fold iodine concentration of the total body (calculated from the contents of the fractions), and a significantly increased thyroid weight compared to the group without supplementary iodine. Iodine supplementation increased iodine content in thyroid and bones significantly (P < 0.05) but not in innards/blood. On an average of the groups, the thyroid contained 80% of the body’s iodine, innards/blood 14%, muscle/fat 5% and bones 1%.The iodine content of pork, and consequently its contribution to human iodine supply (∼1%), is very low, even at high supplementation of feed. The total body iodine content (empty body) is determined by the iodine intake. Irrespective of the iodine dosage, the thyroid contains about 4/5 of the body iodine. Bones represent a very low iodine concentration, even at a strongly increased iodine intake. The increase of the thyroid weight as an adverse effect of iodine supplementation requires further research with high dietary iodine.
Keywords: iodine; distribution; muscle/fat; innards/blood; bone; growing pigs

Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism by Ewa Jablonska; Jolanta Gromadzinska; Wojciech Sobala; Edyta Reszka; Wojciech Wasowicz (47-54).
Selenium (Se) is a trace element suggested to act chemopreventive in lung cancer. The mechanism by which Se suppresses tumour development may be associated with some of the functions of selenoproteins, including 15 kDa selenoprotein (Sep15). This protein exhibits antioxidant properties and thus may be involved in the process of carcinogenesis. Recently, it has been shown that the genetic polymorphism of Sep15, resulting in different response of the protein to Se, is associated with the risk of breast and head and neck cancers.The aim of the study was to investigate the possible association between lung cancer risk and Sep15 polymorphism in combination with Se status in the Polish population.The study concerned 325 cases and 287 controls. All the participants were smokers. Plasma Se concentration was determined using graphite furnace atomic absorption spectrometry, and Sep15 polymorphism (1125 G/A transition within 3′-untranslated region) was detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.The adjusted odds ratios (ORs) for lung cancer cases, compared to individuals with Sep15 wild type variant (GG), were: 0.91 (95% CI: 0.64–1.32) for the heterozygous variant (GA) and 0.80 (95% CI: 0.39–1.65) for the homozygous variant (AA). Although plasma Se concentration was statistically lower in lung cancer cases (49.4 ± 17.4 ng/ml) compared to controls (53.3 ± 14.0 ng/ml, p < 0.002), the analysis of the joint effect of Sep15 polymorphism and Se status for lung cancer development revealed that lung cancer risk differed between the Se15 genotype groups. An increasing Se concentration was associated with a decreased risk in all individuals; however, at Se concentration above 80 ng/ml, the risk started to increase in individuals possessing the Sep15 1125 GG or GA genotype.It appears that among smoking individuals, those with the Sep15 1125 AA genotype may benefit most from a higher Se intake, whereas in those with the GG or GA genotype, a higher Se status may increase the risk for lung cancer.
Keywords: Sep15 ; selenium; lung cancer

Suitability of 3-point versus 7-point postprandial retinyl palmitate AUC in human bioavailability studies by Carmen Herrero-Barbudo; Fernando Granado-Lorencio; Begoña Olmedilla-Alonso (55-58).
Bioavailability is a critical feature in the assessment of the role of micronutrients in human health. Although postprandial behaviour does not predict long-term responses and acute responses, it is accepted that the study of triglyceride-rich lipoprotein fractions reflects newly absorbed lipids from recent meals.To assess the predictive value of a 3-point versus 7-point post-prandial response (area under the curve) in nutrient bioavailability studies in humans.We used results from a human bioavailability study (n = 19) that consisted of a single-dose pharmacokinetic assay involving three types of commercially available vitamin A and E fortified milk.Correlation coefficients between 3-point AUC (AUCp, predictive) versus 7-point AUC (AUCc, conventional) ranged between r = 0.81 (P < 0.001) for vitamin A-fortified skim milk and r = 0.95 (P < 0.001) for whole milk. Bland-Altman representations showed a good agreement between the two methods with 95% of the differences within the concordance limits. More than 90% of the subjects were correctly classified in the same or adjacent quartiles and he calculated relative absorption of vitamin A from the foods was, on average, <5% lower using the AUCp compared to that estimated using AUCc.The use of the 3-point approach may be a reliable alternative to assess the relative postprandial lipid response in human bioavailability studies. Nevertheless, since this approach has been studied considering one nutrient (i.e. preformed vitamin A) and one type of food (i.e. milk), its applicability to other nutrients and foods should be tested.
Keywords: bio availability; vitamin A; human study; area under the curve