Effect of investigative laparoscopy on bladder pain syndrome: a prospective cohort trial.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain is a debilitating condition, and establishing both an etiology and a successful management plan is challenging. Bladder pain syndrome (BPS) is one such etiology, with some studies reporting a prevalence of up to 50% in women with chronic pelvic pain (Van De Merwe et al. Eur Urol 53: 60-67, 2008; Cervigni and Natale Int J Urol 21: 85-88, 2014). This study aimed to assess the impact that investigative laparoscopy with treatment of endometriosis has on bladder pain syndrome in women with and without endometriosis. METHODS: A prospective cohort study was conducted with participants recruited from a tertiary gynecology unit and the private rooms of participating gynecologists. Women included were those scheduled for laparoscopy for investigation of pelvic pain of > 6 months, aged 18-40 years. Each patient completed a preoperative questionnaire, and a standardized study operative report was used to collect laparoscopy findings. Any endometriosis found was treated with excisional surgery. Patients were then reviewed with the same questionnaire at 3, 6 and 12 months post-surgery. RESULTS: A total of 150 patients were included in the trial. Seventy-five percent of patients (n = 112/150) were diagnosed with endometriosis. Of them, 43% (n = 48/112) also had BPS. The overall BPS rate was 43% (n = 64/150). At 12 months, there was a significant reduction in overall pain and pelvic pain in all groups. Of the women with BPS, there was no difference in symptom score reduction between those with endometriosis treated and those without endometriosis. BPS resolved in 42% of women 12 months post-laparoscopy, regardless of whether endometriosis was diagnosed and treated or not. Of the women without BPS preoperatively, 14% developed de novo BPS at 12 months, regardless of whether endometriosis was diagnosed and treated or not. CONCLUSION: Our findings show that BPS improves in the 12 months after investigative laparoscopy and treatment of endometriosis for chronic pelvic pain, regardless of presence or absence of endometriosis.

Systematic review using meta-analyses to estimate dose-response relationships between iodine intake and biomarkers of iodine status in different population groups.

The objective of this systematic review was to identify studies investigating iodine intake and biomarkers of iodine status, to assess the data of the selected studies, and to estimate dose-response relationships using meta-analysis. All randomized controlled trials, prospective cohort studies, nested case-control studies, and cross-sectional studies that supplied or measured dietary iodine and measured iodine biomarkers were included. The overall pooled regression coefficient (ß) and the standard error of ß were calculated by random-effects meta-analysis on a double-log scale, using the calculated intake-status regression coefficient (ß) for each individual study. The results of pooled randomized controlled trials indicated that the doubling of dietary iodine intake increased urinary iodine concentrations by 14% in children and adolescents, by 57% in adults and the elderly, and by 81% in pregnant women. The dose-response relationship between iodine intake and biomarkers of iodine status indicated a 12% decrease in thyroid-stimulating hormone and a 31% decrease in thyroglobulin in pregnant women. The model of dose-response quantification used to describe the relationship between iodine intake and biomarkers of iodine status may be useful for providing complementary evidence to support recommendations for iodine intake in different population groups.

Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials.

BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake. OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake. DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (ß) for individual studies and the overall pooled ß were calculated by using random-effects meta-analysis. RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 µg/d. Calculation of the overall pooled ß for studies in the range of 50 to 400 µg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate. CONCLUSIONS: Studies administering >400 µg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

EURRECA-Evidence-based methodology for deriving micronutrient recommendations.

The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one "Defining the problem" describes Activities 1 and 2: "Identifying the nutrition-related health problem" and "Defining the process"; stage two "Monitoring and evaluating" describes Activities 3 and 7: "Establishing appropriate methods," and "Nutrient intake and status of population groups"; stage three "Deriving dietary reference values" describes Activities 4, 5, and 6: "Collating sources of evidence," "Appraisal of the evidence," and "Integrating the evidence"; stage four "Using dietary reference values in policy making" describes Activities 8 and 9: "Identifying policy options," and "Evaluating policy implementation." These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.].

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-Estimating selenium requirements for deriving dietary reference values.

Current reference values for selenium, an essential micronutrient, are based on the intake of selenium that is required to achieve maximal glutathione peroxidase activity in plasma or erythrocytes. In order to assess the evidence of relevance to setting dietary reference values for selenium, the EURRECA Network of Excellence focused on systematic searches, review, and evaluation of (i) selenium status biomarkers and evidence for relationships between intake and status biomarkers, (ii) selenium and health (including the effect of intake and/or status biomarkers on cancer risk, immune function, HIV, cognition, and fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of genotype/single nucleotide polymorphisms on status or health outcomes associated with selenium. The main research outputs for selenium and future research priorities are discussed further in this review.

EURRECA-Estimating zinc requirements for deriving dietary reference values.

Zinc was selected as a priority micronutrient for EURRECA, because there is significant heterogeneity in the Dietary Reference Values (DRVs) across Europe. In addition, the prevalence of inadequate zinc intakes was thought to be high among all population groups worldwide, and the public health concern is considerable. In accordance with the EURRECA consortium principles and protocols, a series of literature reviews were undertaken in order to develop best practice guidelines for assessing dietary zinc intake and zinc status. These were incorporated into subsequent literature search strategies and protocols for studies investigating the relationships between zinc intake, status and health, as well as studies relating to the factorial approach (including bioavailability) for setting dietary recommendations. EMBASE (Ovid), Cochrane Library CENTRAL, and MEDLINE (Ovid) databases were searched for studies published up to February 2010 and collated into a series of Endnote databases that are available for the use of future DRV panels. Meta-analyses of data extracted from these publications were performed where possible in order to address specific questions relating to factors affecting dietary recommendations. This review has highlighted the need for more high quality studies to address gaps in current knowledge, in particular the continued search for a reliable biomarker of zinc status and the influence of genetic polymorphisms on individual dietary requirements. In addition, there is a need to further develop models of the effect of dietary inhibitors of zinc absorption and their impact on population dietary zinc requirements.

The absorption of iron from whole diets: a systematic review.

BACKGROUND: Absorption factors are required to convert physiologic requirements for iron into Dietary Reference Values, but the absorption from single meals cannot be used to estimate dietary iron absorption. OBJECTIVE: The objective was to conduct a systematic review of iron absorption from whole diets. DESIGN: A structured search was completed by using the Medline, EMBASE, and Cochrane CENTRAL databases from inception to November 2011. Formal inclusion and exclusion criteria were applied, and data extraction, validity assessment, and meta-analyses were undertaken. RESULTS: Nineteen studies from the United States, Europe, and Mexico were included. Absorption from diets was higher with an enhancer (standard mean difference: 0.53; 95% CI: 0.21, 0.85; P = 0.001) and was also higher when compared with low-bioavailability diets (standard mean difference: 0.96; 95% CI: 0.51, 1.41; P < 0.0001); however, single inhibitors did not reduce absorption (possibly because of the limited number of studies and participants and their heterogeneity). A regression equation to calculate iron absorption was derived by pooling data for iron status (serum and plasma ferritin) and dietary enhancers and inhibitors from 58 individuals (all from US studies): log[nonheme-iron absorption, %] = -0.73 log[ferritin, µg/L] + 0.11 [modifier] + 1.82. In individuals with serum ferritin concentrations from 6 to 80 µg/L, predicted absorption ranged from 2.1% to 23.0%. CONCLUSIONS: Large variations were observed in mean nonheme-iron absorption (0.7-22.9%) between studies, which depended on iron status (diet had a greater effect at low serum and plasma ferritin concentrations) and dietary enhancers and inhibitors. Iron absorption was predicted from serum ferritin concentrations and dietary modifiers by using a regression equation. Extrapolation of these findings to developing countries and to men and women of different ages will require additional high-quality controlled trials.

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.

Selenium and prostate cancer: systematic review and meta-analysis.

BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent. OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk. DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk. RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 µg/g. CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.

Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.

Selenium in human health and disease.

This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

Risk-benefit analysis of mineral intakes: case studies on copper and iron.

Dietary reference values for essential trace elements are designed to meet requirements with minimal risk of deficiency and toxicity. Risk-benefit analysis requires data on habitual dietary intakes, an estimate of variation and effects of deficiency and excess on health. For some nutrients, the range between the upper and lower limits may be extremely narrow and even overlap, which creates difficulties when setting safety margins. A new approach for estimating optimal intakes, taking into account several health biomarkers, has been developed and applied to selenium, but at present there are insufficient data to extend this technique to other micronutrients. The existing methods for deriving reference values for Cu and Fe are described. For Cu, there are no sensitive biomarkers of status or health relating to marginal deficiency or toxicity, despite the well-characterised genetic disorders of Menkes and Wilson's disease which, if untreated, lead to lethal deficiency and overload, respectively. For Fe, the wide variation in bioavailability confounds the relationship between intake and status and complicates risk-benefit analysis. As with Cu, health effects associated with deficiency or toxicity are not easy to quantify, therefore status is the most accessible variable for risk-benefit analysis. Serum ferritin reflects Fe stores but is affected by infection/inflammation, and therefore additional biomarkers are generally employed to measure and assess Fe status. Characterising the relationship between health and dietary intake is problematic for both these trace elements due to the confounding effects of bioavailability, inadequate biomarkers of status and a lack of sensitive and specific biomarkers for health outcomes.

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.

Selenium bioavailability: current knowledge and future research requirements.

Information on selenium bioavailability is required to derive dietary recommendations and to evaluate and improve the quality of food products. The need for robust data is particularly important in light of recent suggestions of potential health benefits associated with different intakes of selenium. The issue is not straightforward, however, because of large variations in the selenium content of foods (determined by a combination of geologic/environmental factors and selenium supplementation of fertilizers and animal feedstuffs) and the chemical forms of the element, which are absorbed and metabolized differently. Although most dietary selenium is absorbed efficiently, the retention of organic forms is higher than that of inorganic forms. There are also complications in the assessment and quantification of selenium species within foodstuffs. Often, extraction is only partial, and the process can alter the form or forms present in the food. Efforts to improve, standardize, and make more widely available techniques for species quantification are required. Similarly, reliable and sensitive functional biomarkers of selenium status are required, together with improvements in current biomarker methods. This requirement is particularly important for the assessment of bioavailability, because some functional biomarkers respond differently to the various selenium species. The effect of genotype adds a potential further dimension to the process of deriving bioavailability estimates and underlines the need for further research to facilitate the process of deriving dietary recommendations in the future.

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.

Estimating the bioavailability factors needed for setting dietary reference values.

Estimated average requirements for micronutrients are central to deriving Dietary Reference Values. These are used for nutrition policies and programs, and also for regulatory and labeling purposes, and are traditionally devised to cover the needs of virtually all individuals in any population group. In order to estimate the average requirement, an appropriate endpoint (biomarker) is selected which describes the relationship between dietary intake and health. However, for some micronutrients, such as zinc, there are no good biomarkers, and for others, such as iron, the intake-status relationship is confounded by variations in absorption. Average requirements for these nutrients are derived using a factorial approach in which physiological needs for tissue growth and maintenance and endogenous losses are estimated, and the total converted to a dietary requirement by taking into account the overall absorption from the diet; i. e. multiplying the requirement by a bioavailability factor. The latter can be determined using algorithms, or estimates from absorption studies, some of which are described in this short review paper.

Plasma hepcidin concentrations significantly predict interindividual variation in iron absorption in healthy men.

BACKGROUND: Iron absorption is proposed to be regulated by circulating hepcidin, but, to date, little data are available to evaluate this relation in humans. OBJECTIVE: Stored samples from a human iron absorption study were used to test the hypothesis that differences in plasma hepcidin explain interindividual variation in iron absorption. DESIGN: Hepcidin-25 concentrations were measured in fasting samples from men aged > or = 40 y (n = 33) recruited to a study investigating the relation between the HFE genotype, iron absorption, and iron status. RESULTS: Log iron absorption was negatively correlated with serum ferritin (r = -0.59, P < 0.001) and with plasma hepcidin (r = -0.55, P < 0.001) but was unaffected by genotype. There was a positive correlation (r = 0.82, P < 0.001) between hepcidin (mean: 2.3; range: 0.1-7.8 nmol/L) and ferritin (mean: 70; range: 9-208 microg/L). Multiple linear regression models showed that plasma hepcidin in isolation significantly predicted 36% of the interindividual variation in iron absorption. CONCLUSIONS: Plasma hepcidin and serum ferritin concentrations are highly correlated, and, in the normal range of plasma hepcidin values, 36% of interindividual differences in iron absorption are explained by differences in circulating plasma hepcidin.

Relative bioavailability of micronized, dispersible ferric pyrophosphate added to an apple juice drink.

BACKGROUND: Food iron fortification is a sustainable and relatively simple strategy to reduce/prevent iron deficiency but is a challenge for the food industry because of possible adverse organoleptic changes caused by the added iron. A micronized dispersible ferric pyrophosphate, trademarked as SunActive Fe, has recently been developed. SunActive Fe has a small particle size, is water soluble and may be suitable for fortifying liquid products. AIM OF THE STUDY: To determine the relative bioavailability of SunActive Fe and its suitability for addition to pure apple juice. METHODS: Iron absorption from SunActive Fe added to pure apple juice (Minute Maid) was compared with absorption from ferrous sulphate, a highly bioavailable form of iron, in 15 women with relatively low iron stores. Both forms of iron were enriched with an iron stable isotope and iron absorption from the apple juice drinks was calculated from the isotopic enrichment of red blood cells 14 days after the last test meal. RESULTS: Although mean absorption of iron from SunActive Fe was significantly lower than from ferrous sulphate (5.5% compared with 9.1%), the mean bioavailability of SunActive Fe iron relative to ferrous sulphate was 0.6, indicating that it is a good source of bioavailable iron. Iron Absorption from SunActive Fe was positively correlated (r = 0.97, P = 0.01) with absorption from ferrous sulphate, and negatively correlated with serum ferritin concentration (ferrous sulphate r = -0.81, P < 0.001; SunActive Fe r = -0.76, P = 0.01). CONCLUSIONS: SunActive Fe was well absorbed from apple juice and is a potentially useful fortificant for liquid food products.