The relationship between zinc intake and serum/plasma zinc concentration in adults: a systematic review and dose–response meta-analysis by the EURRECA Network

Dietary zinc recommendations vary widely across Europe due to the heterogeneity of pproaches used by expert panels. Under the EURRECA consortium a protocol was designed to systematically review and undertake meta-analyses of research data to create a database that includes “best practice” guidelines which can be used as a resource by future panels when setting micronutrient recommendations. As part of this process, the objective of the present study was to undertake a systematic review and meta-analysis of previously published data describing the relationship between zinc intake and status in adults. Searches were performed of literature published up to February 2010 using MEDLINE, Embase, and Cochrane Library. Data extracted included population characteristics, dose of zinc, duration of study, dietary intake of zinc, and mean concentration of zinc in plasma or serum at the end of the intervention period. An intake-status regression coefficient was estimated for each individual study, and pooled meta-analysis undertaken. The overall pooled for zinc supplementation on serum/plasma zinc concentrations from RCTs and observational studies was 0.08 (95% CI 0.05, 0.11; p<0.0001; I2 84.5%). An overall of 0.08 means that for every doubling in zinc intake, the difference in zinc serum or plasma concentration is (20.08 = 1.06), which is 6%. Whether the dose-response relationship, as provided in this paper, could be used as either qualitative or quantitative evidence to substantiate the daily zinc intake dose necessary to achieve normal or optimal levels of biomarkers for zinc status, remains a matter of discussion

Estimating effects of rare haplotypes on failure time using a penalized Cox proportional hazards regression model

BACKGROUND: This paper describes a likelihood approach to model the relation between failure time and haplotypes in studies with unrelated individuals where haplotype phase is unknown, while dealing with the problem of unstable estimates due to rare haplotypes by considering a penalized log-likelihood. RESULTS: The Cox model presented here incorporates the uncertainty related to the unknown phase of multiple heterozygous individuals as weights. Estimation is performed with an EM algorithm. In the E-step the weights are estimated, and in the M-step the parameter estimates are estimated by maximizing the expectation of the joint log-likelihood, and the baseline hazard function and haplotype frequencies are calculated. These steps are iterated until the parameter estimates converge. Two penalty functions are considered, namely the ridge penalty and a difference penalty, which is based on the assumption that similar haplotypes show similar effects. Simulations were conducted to investigate properties of the method, and the association between IL10 haplotypes and risk of target vessel revascularization was investigated in 2653 patients from the GENDER study. CONCLUSION: Results from simulations and real data show that the penalized log-likelihood approach produces valid results, indicating that this method is of interest when studying the association between rare haplotypes and failure time in studies of unrelated individuals

The Relationship between Zinc Intake and Serum/Plasma Zinc Concentration in Children: A Systematic Review and Dose-Response Meta-Analysis

Recommendations for zinc intake during childhood vary widely across Europe. The EURRECA project attempts to consolidate the basis for the definition of micronutrient requirements, taking into account relationships among intake, status and health outcomes, in order to harmonise these recommendations. Data on zinc intake and biomarkers of zinc status reported in randomised controlled trials (RCTs) can provide estimates of dose-response relationships which may be used for underpinning zinc reference values. This systematic review included all RCTs of apparently healthy children aged 1–17 years published by February 2010 which provided data on zinc intake and biomarkers of zinc status. An intake-status regression coefficient was calculated for each individual study and calculated the overall pooled and SE using random effects meta-analysis on a double log scale. The pooled dose-response relationship between zinc intake and zinc status indicated that a doubling of the zinc intake increased the serum/plasma zinc status by 9%. This evidence can be utilised, together with currently used balance studies and repletion/depletion studies, when setting zinc recommendations as a basis for nutrition policies

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.]This is the peer-reviewed version of the article: Dhonukshe-Rutten Rosalie, Bouwman Jildau, Brown Kerry A., Cavelaars Adrienne E., Collings Rachel, Grammatikaki Evangelia, de Groot Lisette, Gurinović Mirjana A., Harvey Linda, Hermoso Maria, Hurst Rachel, Kremer Bas, Ngo Joy, Novaković Romana, Raats Monique M., Rollin Fanny, Serra-Majem Lluis, Souverein Olga W., Timotijević Lada, van't Veer Pieter, "EURRECA-Evidence-Based Methodology for Deriving Micronutrient Recommendations" 53, no. 10 (2013):999-1040, [https://doi.org/10.1080/10408398.2012.749209

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.This is the peer-reviewed version of the article: Lowe Nicola M., Dykes Fiona C., Skinner Anna-Louise, Patel Sujata, Warthon-Medina Marisol, Decsi Tamas, Fekete Katalin, Souverein Olga W., Dullemeijer Carla, Cavelaars Adrienne E., Serra-Majem Lluis, Nissensohn Mariela, Bel Silvia, Moreno Luis A., Hermoso Maria, Vollhardt Christiane, Berti Cristiana, Cetin Irene, Gurinović Mirjana A., Novaković Romana, Harvey Linda, Collings Rachel, Hall-Moran Victoria, "EURRECA-Estimating Zinc Requirements for Deriving Dietary Reference Values" 53, no. 10 (2013):1110-1123, [https://doi.org/10.1080/10408398.2012.742863

Polymorphisms in APOA1 and LPL genes are statistically independently associated with fasting TG in men with CAD

The objective of this paper was to identify the single nucleotide polymorphisms ( SNPs) that show unshared effects on plasma triglyceride (TG) levels and to investigate whether these SNPs show statistically independent effects on plasma TG levels. In total, 59 polymorphisms in 20 genes involved in lipid metabolism were investigated. Polymorphisms were selected for a multivariate ANOVA model if they showed an univariate association with TG ( after adjustment for HDL-C and LDL-C) in more than 50% of bootstrap samples that were made from the original data. The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure (ie, APOA1 G( - 75) A, ABCA1 C( - 477) T, ABCA1 G1051A, APOC3 T3206G, APOE Arg158Cys, LIPC C( - 514) T, LPL Asn291Ser and LPL Ser447Stop). The gene variants APOA1 G( - 75) A ( P = 0.04) and LPL Asn291Ser ( P = 0.03) were significantly associated with plasma TG levels in this multivariate analysis. The eight polymorphisms explained 8.9% of the variation in plasma TG levels. In conclusion, this study showed statistically independent effects of gene variants in the APOA1 and LPL genes on fasting plasma levels of TG. Nevertheless, only a small part of variation in TG levels could be explained by the polymorphism

Influence of LDL-receptor mutation type on age at first cardiovascular event in patients with familial hypercholesterolaemia

AIMS: To investigate the influence of different LDL-receptor (LDLR) gene mutations on age at first cardiovascular event in familial hypercholesterolaemia (FH) patients. METHODS AND RESULTS: Dutch FH patients (n = 862) with known LDLR mutations from a retrospective cohort study were included. A gamma frailty Cox model was used. An event was defined as the first cardiovascular event. Gender, hypertension, smoking, diabetes, HDL cholesterol, LDL cholesterol (LDL-C), or triglycerides were included as covariates. Furthermore, the effect of LDLR mutation type on LDL and HDL cholesterol levels was investigated using mixed effects models, including gender, smoking, body mass index, and age at time of lipid measurement as covariates. A total of 86 different LDLR mutations were present in this cohort. Twenty-two percent of patients experienced an event (median age: 47.1 year; range: 25.6-85.8 years). The effect of LDLR mutation type on event-free survival is only significant in the models without LDL-C levels. Also, LDLR mutation type was significantly associated with LDL-C levels (P = 0.007), but not with HDL cholesterol levels (P = 0.12). CONCLUSION: In the present study, LDL-C levels are a more important risk factor of event-free survival than the type of LDLR mutatio