Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: a randomized controlled trial.

We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and 100mg epicatechin (low and high flavanol apple puree, respectively) and aspirin (75 mg) in random order. Measurements were made at baseline, acutely after treatment (2, 6 and 24 h), and after 14 d of treatment. Low flavanol apple puree significantly attenuated ADP and epinephrine-induced integrin-ß3 expression 2 h and 6 h after consumption and ADP and epinephrine-induced P-selectin expression within 2h of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced integrin-ß3 expression after 2 and 6h. ADP and epinephrine-induced integrin-ß3 expression was significantly attenuated 2, 6 and 24 h after consumption of aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin expression only. The plasma total nitric oxide metabolite conc. was significantly increased 6h after consumption of both low and high flavanol apple purees. In conclusion, consumption of apple purees containing ⩾25 or 100 mg flavanols transiently attenuated ex vivo integrin-ß3 and P-selectin expression and increased plasma nitric oxide metabolite conc. in healthy subjects, but the effect was not enhanced for the high flavanol apple puree.

EURRECA-Estimating iron requirements for deriving dietary reference values.

Currently, a factorial approach is used to derive reference values for iron. Calculations include the use of a bioavailability factor to convert the physiological requirement, derived from obligatory losses and requirements for growth and development, into a dietary intake value. A series of systematic reviews undertaken by the EURRECA Network of Excellence aimed to identify data that may increase the accuracy of factorial calculations across all population groups. The selection of robust data was guided by the use of standardized review methodology and the evidence-based selection of status biomarkers and dietary intake assessment techniques. Results corroborated the dearth of relevant factorial data, including whole-diet bioavailability data, and confirmed the need to continue extrapolating physiological requirements across population groups. Data were also unavailable that would allow reference values to be based on selected health outcomes associated with iron intake or status. Ideally, a series of observational and randomized controlled trial (RCT) studies need to be undertaken across all population groups and life stages to generate robust data for setting dietary reference values for iron. It will also be essential to include information on polymorphisms that potentially influence iron absorption and status in the derivation process.

EURRECA's approach for estimating micronutrient requirements.

In Europe, micronutrient dietary reference values have been established by (inter)national committees of experts and are used by public health policy decision-makers to monitor and assess the adequacy of diets within population groups. The approaches used to derive dietary reference values (including average requirements) vary considerably across countries, and so far no evidence-based reason has been identified for this variation. Nutrient requirements are traditionally based on the minimum amount of a nutrient needed by an individual to avoid deficiency, and is defined by the body's physiological needs. Alternatively the requirement can be defined as the intake at which health is optimal, including the prevention of chronic diet-related diseases. Both approaches are confronted with many challenges (e. g., bioavailability, inter and intra-individual variability). EURRECA has derived a transparent approach for the quantitative integration of evidence on Intake-Status-Health associations and/or Factorial approach (including bioavailability) estimates. To facilitate the derivation of dietary reference values, EURopean micronutrient RECommendations Aligned (EURRECA) is developing a process flow chart to guide nutrient requirement-setting bodies through the process of setting dietary reference values, which aims to facilitate the scientific alignment of deriving these values.

Effect of iron intake on iron status: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The response of status biomarkers to an increase in iron supply depends on several physiologic and environmental factors, which make it difficult to predict the outcome of an intervention. OBJECTIVE: We assessed effects of baseline iron status, sex, menopausal status, duration of intervention, iron form, and daily dose on the change in iron status in response to iron supplementation. DESIGN: A systematic review of randomized controlled trials (RCTs) of iron-supplementation and -fortification trials that assessed effects on hemoglobin, serum ferritin (SF), soluble transferrin receptor, or body iron was conducted. Subgrouping and straight-line and curved metaregression were used to describe the magnitude and dose-responsiveness of effect modifiers with respect to changes in status. RESULTS: Forty-one RCTs were included; none of the RCTs were judged at low risk of bias. Random-effects meta-analyses showed that iron supplementation significantly improved iron status but with high levels of heterogeneity. Metaregression explained approximately one-quarter of between-study variance in effect size. There were clear effects on SF with study duration (increase in SF concentration/wk: 0.51 µg/L; 95% CI: 0.02, 1.00 µg/L; P = 0.04) and dose (increase in SF concentration/g Fe: 0.10 µg/L; 95% CI: 0.01, 0.20 µg/L; P = 0.036) and on hemoglobin concentrations with baseline iron status [-0.08 g/dL (95% CI: 0.15, 0.00 g/dL) per 10-µg/L increase in baseline SF concentration; P = 0.02]. Insufficient data were available to assess effects on body iron, sex, or menopausal status. CONCLUSION: Quantitative relations between baseline iron status, study duration, and iron dose on changes in iron-status biomarkers, which were generated from the meta-analyses, can be used to predict effects of trials of iron supplementation and fortification and to design iron-intervention programs.

Micronutrient bioavailability research priorities.

A micronutrient bioavailability workshop, which involved international experts and members of the scientific community and the food industry, with interactive breakout sessions based on synectics principles, was organized by the International Life Sciences Institute Europe Addition of Nutrients to Food Task Force and the European Commission Network of Excellence European Micronutrient Recommendations Aligned. After presentations by experts, a series of "challenge statements" was discussed. The aim was to address topical issues, in particular those that linked bioavailability with the derivation of micronutrient requirements and dietary recommendations, to identify gaps in knowledge and to consider research priorities. Several generic research priorities were identified, including improving the quality of dietary surveys/food composition tables, the need for more metabolic studies that use stable isotopes and high-quality longer-term interventions, and the development of multifactorial mathematical models. Among the common recurrent factors identified as important were polymorphisms/genotype, consideration of the whole diet, chemical form of the micronutrient, and the determination of physiologic requirements. The involvement of all participants in the structured discussions ensured a broad overview of current knowledge, state-of-the-art research, and consideration of priorities for future research.

Methods of assessment of iodine status in humans: a systematic review.

BACKGROUND: Biomarkers of iodine status are required to study iodine deficiency disorders in different parts of the world and to evaluate the effects of fortification strategies. OBJECTIVE: The objective was to assess the usefulness of biomarkers of iodine status in humans by systematically reviewing intervention studies that altered iodine status. DESIGN: We performed a structured search for iodine intervention studies on Ovid MEDLINE, EMBASE (Ovid), and the Cochrane Library. Studies were assessed for inclusion and validity, with independent duplication. A random-effects meta-analysis was performed. RESULTS: Twenty-one intervention studies (12 randomized controlled trials, 3 controlled clinical trials, and 6 before-after studies) were included in the review. Urinary iodine (in children and adolescents and in those with low and moderate baseline iodine status), thyroglobulin (in children and adolescents but not in pregnant and lactating women), serum thyroxine (in children and adolescents, adults, women, and those with moderate baseline thyroxine status but not in pregnant and lactating women), and serum thyroid-stimulating hormone (in pregnant and lactating women but not in children and adolescents or those at moderate baseline status), but not triiodothyronine, proved to be useful biomarkers of iodine status. CONCLUSIONS: Despite the high risk of bias of many of the included studies, the results suggested that urinary iodine, thyroglobin, serum thyroxine, and thyroid-stimulating hormone are useful biomarkers of iodine status, at least in some groups. High-quality controlled studies measuring relevant long-term outcomes are needed to address which biomarker is the most appropriate for assessing iodine intake in some population groups and settings.

Methods of assessment of copper status in humans: a systematic review.

BACKGROUND: The assessment of dietary adequacy of copper is constrained by the absence of recognized copper status biomarkers. OBJECTIVES: The objectives were to systematically review the usefulness of copper status biomarkers and identify those that reflected changes in status over > or =4 wk. DESIGN: The methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases to October 2007, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis. RESULTS: A total of 16 studies (288 participants) were included in the review, with data on 16 possible copper biomarkers. All of the included studies were small and at high risk of bias. Data for serum copper suggested its value as a biomarker, reflecting changes in status in both depleted and replete individuals, although these changes were smaller in the latter. Total ceruloplasmin protein is related to copper status but reflects changes in highly depleted individuals only. Erythrocyte superoxide dismutase and urinary deoxypyridinoline are not useful biomarkers, but there were insufficient data to draw firm conclusions about plasma, erythrocyte, and platelet copper; leukocyte superoxide dismutase; erythrocyte, platelet, and plasma glutathione peroxidase; platelet and leukocyte cytochrome-c oxidase; total glutathione; diamine oxidase; and urinary pyridinoline. The paucity of data prevented detailed subgroup analysis. CONCLUSIONS: Despite limited data, serum copper appears to be a useful biomarker of copper status at the population level. Further large studies with low risk of bias are needed to explore the effectiveness of other biomarkers of copper status and the relation between biomarker responsiveness, dose, and period of supplementation.

Methods of assessment of selenium status in humans: a systematic review.

BACKGROUND: To understand the effect of selenium intake on health, it is important to identify sensitive and population-specific biomarkers of selenium status. OBJECTIVE: The objective of this systematic review was to assess the usefulness of biomarkers of selenium status in humans. DESIGN: The methods included a structured search strategy on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction into an Access database; validity assessment; and meta-analysis. RESULTS: The data from 18 selenium supplementation studies (of which 9 were randomized controlled trials and 1 was considered to be at low risk of bias) indicate that plasma, erythrocyte, and whole-blood selenium, plasma selenoprotein P, and plasma, platelet, and whole-blood glutathione peroxidase activity respond to changes in selenium intake. Although there is a substantial body of data for plasma selenium, more large, high-quality, randomized controlled trials are needed for this biomarker, as well as for the other biomarkers, to explore the reasons for heterogeneity in response to selenium supplementation. There was insufficient evidence to assess the usefulness of other potential biomarkers of selenium status, including urinary selenium, plasma triiodothyroxine:thyroxine ratio, plasma thyroxine, plasma total homocysteine, hair and toenail selenium, erythrocyte, and muscle glutathione peroxidase activity. CONCLUSIONS: For all potentially useful biomarkers, more information is needed to evaluate their strengths and limitations in different population groups, including the effects of varying intakes, the duration of intervention, baseline selenium status, and possible confounding effects of genotype.