NUQUEST-NUtrition QUality Evaluation Strengthening Tools: development of tools for the evaluation of risk of bias in nutrition studies.

Background: Dietary exposure assessments are a critical issue in evaluating human nutrition studies; however, nutrition-specific criteria are not consistently included in existing bias assessment tools.

Objectives: Our objective was to develop a set of risk of bias (RoB) tools that integrated nutrition-specific criteria into validated generic assessment tools to address RoB issues, including those specific to dietary exposure assessment.

Methods: The Nutrition QUality Evaluation Strengthening Tools (NUQUEST) development and validation process included 8 steps.

Surrogate disease markers as substitutes for chronic disease outcomes in studies of diet and chronic disease relations.

Surrogate biomarkers for clinical outcomes afford scientific and economic efficiencies when investigating nutritional interventions in chronic diseases. However, valid scientific results are dependent on the qualification of these disease markers that are intended to be substitutes for a clinical outcome and to accurately predict benefit or harm. In this article, we examine the challenges of evaluating surrogate markers and describe the framework proposed in a 2010 Institute of Medicine report.

Correspondence of folate dietary intake and biomarker data.

Public health concerns with regard to both low and high folate status exist in the United States. Recent publications have questioned the utility of self-reported dietary intake data in research and monitoring. The purpose of this analysis was to examine the relation between self-reported folate intakes and folate status biomarkers and to evaluate their usefulness for several types of applications.

Challenges and Lessons Learned in Generating and Interpreting NHANES Nutritional Biomarker Data.

For the past 45 y, the National Center for Health Statistics at the CDC has carried out nutrition surveillance of the US population by collecting anthropometric, dietary intake, and nutritional biomarker data, the latter being the focus of this publication. The earliest biomarker testing assessed iron and vitamin A status. With time, a broad spectrum of water- and fat-soluble vitamins was added and biomarkers for other types of nutrients (e.

Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group.

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation.

Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population.

Background: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution.

Objective: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs.

The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases.

Background: Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D [25(OH)D] measurements.

Objective: To accurately assess vitamin D status trends among those aged ≥12 y, we used data from the cross-sectional NHANESs.

Design: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446).

Safe use of high intakes of folic acid: research challenges and paths forward.

Adequate folic acid intake is an effective dietary-based prevention tool for reducing the risk of neural tube defects. Achieving adequate intake for the prevention of neural tube defects frequently requires the consumption of foods fortified with folic acid and/or the use of folic acid-containing dietary supplements. To date, research on the potential for adverse effects of high intakes of folic acid has been limited.

A Method-bridging Study for Serum 25-hydroxyvitamin D to Standardize Historical Radioimmunoassay Data to Liquid Chromatography-Tandem Mass Spectrometry.

Background: Serum concentrations of 25-hydroxyvitamin D (25OHD) were measured for the National Health and Nutrition Examination Survey (NHANES) over the 1988-2006 period using a radioimmunoassay (RIA). In 2010, the Centers for Disease Control and Prevention (CDC) reissued RIA-harmonized 25OHD for NHANES 2004 and 2006, and advised users to adjust the original RIA data from 1988-1994 by using an equation. Beginning with NHANES 2007-2008, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method measured 25OHD.

National Estimates of Serum Total 25-Hydroxyvitamin D and Metabolite Concentrations Measured by Liquid Chromatography-Tandem Mass Spectrometry in the US Population during 2007-2010.

Background: The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D [25(OH)D] concentrations measured by standardized liquid chromatography-tandem mass spectrometry.

Objective: We describe patterns for total 25(OH)D and individual metabolites in persons aged ≥1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables.

Methods: We measured 25-hydroxycholecalciferol [25(OH)D3], 25-hydroxyergocalciferol [25(OH)D2], and C3-epimer of 25(OH)D3 [C3-epi-25(OH)D3] in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES [total 25(OH)D = 25(OH)D3 + 25(OH)D2].

Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2.

Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC-MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011-2.

Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults.

Background: Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements.

Objectives: We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use.

Including food 25-hydroxyvitamin D in intake estimates may reduce the discrepancy between dietary and serum measures of vitamin D status.

The discrepancy between the commonly used vitamin D status measures-intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations--has been perplexing. Sun exposure increases serum 25(OH)D concentrations and is often used as an explanation for the higher population-based serum concentrations in the face of apparently low vitamin D intake. However, sun exposure may not be the total explanation.

Modeling a methylmalonic acid-derived change point for serum vitamin B-12 for adults in NHANES.

Background: No consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research.

Objective: The study's aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models.

Design: We used data on adults (≥19 y; n = 12,683) from NHANES 1999-2004-a nationally representative, cross-sectional survey.

Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES.

Context: A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).

Objective: Our objective was to repeat the analyses with 6 years additional follow-up to evaluate whether the association persists through 15 years of follow-up.

Participants: The study included 15 099 participants aged ≥ 20 years with 3784 deaths.

Appropriateness of the probability approach with a nutrient status biomarker to assess population inadequacy: a study using vitamin D.

Background: There are questions about the appropriate method for the accurate estimation of the population prevalence of nutrient inadequacy on the basis of a biomarker of nutrient status (BNS).

Objective: We determined the applicability of a statistical probability method to a BNS, specifically serum 25-hydroxyvitamin D [25(OH)D]. The ability to meet required statistical assumptions was the central focus.

Estimation of trends in serum and RBC folate in the U.S. population from pre- to postfortification using assay-adjusted data from the NHANES 1988-2010.

The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations.

Changes in measurement procedure from a radioassay to a microbiologic assay necessitate adjustment of serum and RBC folate concentrations in the U.S. population from the NHANES 1988-2010.

The NHANES measured serum and RBC folate concentrations by using a radioassay during prefortification (1988-1994) and postfortification (1999-2006) periods followed by the use of a microbiologic assay (MBA) from 2007-2010. The MBA produces higher concentrations than does the radioassay and is considered to be more accurate. To allow for accurate long-term trending (1988-2010), we evaluated different regression models (linear, piecewise linear, and fractional polynomial) to assay-adjust the radioassay results to be comparable to the MBA results.

Monitoring folate status in population-based surveys.

Folate status assessments depend primarily on the measurement of biomarkers such as serum and red blood cell folate. Lessons learned from a large national monitoring system such as the National Health and Nutrition Examination Survey and a public health intervention such as the implementation of folic acid fortification in the United States have provided useful insights into the challenges of assessing folate status and possible solutions for addressing these challenges. © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12.

Background: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects.

Objective: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency.

Design: Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612).

Comparison of serum and red blood cell folate microbiologic assays for national population surveys.

Three laboratories participated with their laboratory-specific microbiologic growth assays (MA) in the NHANES 2007-2008 to assess whether the distributions of serum (n = 2645) and RBC folate (n = 2613) for the same one-third sample of participants were comparable among laboratories. Laboratory (L) 2 produced the highest and L1 the lowest serum and RBC folate geometric means (nmol/L) in the NHANES sample (serum: L1, 39.5; L2, 59.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES.

Folate and vitamin B-12 biomarkers in NHANES: history of their measurement and use.

NHANES measured folate and vitamin B-12 status biomarkers, starting with serum folate from NHANES I (1974-1975) through 2010. Subsequent NHANES measured additional biomarkers [eg, red blood cell folate, serum vitamin B-12, total homocysteine (tHcy), methylmalonic acid, serum folic acid, and 5-methyltetrahydrofolic acid]. Examples of the uses of these data are wide ranging and include public policy applications, the derivation of reference intervals, and research.

Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues.

A roundtable dialogue to discuss "NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status" took place in July 2010. This article provides an overview of the meeting and this supplement issue. Although the focus of the roundtable dialogue was on the measurement of folate and vitamin B-12 status biomarkers in NHANES, this article also describes the relevance and importance of these issues for clinical and research laboratories.