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.

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.

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.