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      Folate and vitamin B-12 biomarkers in NHANES: history of their measurement and use 1 2 3 4 5

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          Abstract

          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. Periodically, the National Center for Health Statistics and its federal partners convene expert panels to review the use of the folate- and vitamin B-12–related biomarkers in NHANES. These panels have evaluated the need for results to be comparable across time and with published data and the use of crossover studies and adjustment equations to ensure comparability. With the recent availability of reference methods and materials for serum folate and tHcy, NHANES has started to use traceability approaches to enhance the accuracy and comparability of its results. A major user concern over the years has been the use of cutoffs to estimate the prevalence of inadequate folate and vitamin B-12 status. Because these cutoffs depend on the measurement procedure, several expert panels suggested approaches for dealing with cutoff challenges. This review summarizes the history and use of folate- and vitamin B-12–related biomarkers beginning with NHANES I (1974–1975) through 2010.

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          Most cited references55

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          2000 CDC Growth Charts for the United States: methods and development.

          This report provides detailed information on how the 2000 Centers for Disease Control and Prevention (CDC) growth charts for the United States were developed, expanding upon the report that accompanied the initial release of the charts in 2000. The growth charts were developed with data from five national health examination surveys and limited supplemental data. Smoothed percentile curves were developed in two stages. In the first stage, selected empirical percentiles were smoothed with a variety of parametric and nonparametric procedures. In the second stage, parameters were created to obtain the final curves, additional percentiles and z-scores. The revised charts were evaluated using statistical and graphical measures. The 1977 National Center for Health Statistics (NCHS) growth charts were revised for infants (birth to 36 months) and older children (2 to 20 years). New body mass index-for-age (BMI-for-age) charts were created. Use of national data improved the transition from the infant charts to those for older children. The evaluation of the charts found no large or systematic differences between the smoothed percentiles and the empirical data. The 2000 CDC growth charts were developed with improved data and statistical procedures. Health care providers now have an instrument for growth screening that better represents the racial-ethnic diversity and combination of breast- and formula-feeding in the United States. It is recommended that these charts replace the 1977 NCHS charts when assessing the size and growth patterns of infants, children, and adolescents.
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            Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004.

            Changes in serum 25-hydroxyvitamin D [25(OH)D] concentrations in the US population have not been described. We used data from the National Health and Nutrition Examination Surveys (NHANES) to compare serum 25(OH)D concentrations in the US population in 2000-2004 with those in 1988-1994 and to identify contributing factors. Serum 25(OH)D was measured with a radioimmunoassay kit in 20 289 participants in NHANES 2000-2004 and in 18 158 participants in NHANES III (1988-1994). Body mass index (BMI) was calculated from measured height and weight. Milk intake and sun protection were assessed by questionnaire. Assay differences were assessed by re-analyzing 150 stored serum specimens from NHANES III with the current assay. Age-adjusted mean serum 25(OH)D concentrations were 5-20 nmol/L lower in NHANES 2000-2004 than in NHANES III. After adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 5-9 nmol/L) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH)D concentrations by approximately 10 nmol/L, and adjustment for changes in the factors likely related to real changes in vitamin D status (ie, BMI, milk intake, and sun protection) changed mean serum 25(OH)D concentrations by 1-1.6 nmol/L. Overall, mean serum 25(OH)D was lower in 2000-2004 than 1988-1994. Assay changes unrelated to changes in vitamin D status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status.
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              Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals.

              Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.
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                Author and article information

                Journal
                Am J Clin Nutr
                ajcn
                The American Journal of Clinical Nutrition
                American Society for Nutrition
                0002-9165
                1938-3207
                July 2011
                18 May 2011
                18 May 2011
                : 94
                : 1
                : 322S-331S
                Affiliations
                [1 ]From the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD (EAY); and the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD (CLJ).
                Author notes
                [2]

                Presented at the conference “NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status: a Roundtable Review,” held in Rockville, MD, 15–16 July 2010.

                [3]

                Supported by the Office of Dietary Supplements, National Institutes of Health, and the National Center for Health Statistics, Centers for Disease Control and Prevention.

                [4]

                Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the Centers for Disease Control and Prevention, the National Institutes of Health, or the US Department of Health and Human Services.

                [5 ]Address correspondence to EA Yetley (retired), Office of Dietary Supplements, National Institutes of Health, 6100 Executive Boulevard, Room 3B01, MSC 7517, Bethesda, MD 20892. E-mail: beth@ 123456yetley.com .
                Article
                013300
                10.3945/ajcn.111.013300
                3127520
                21593508
                3d4454af-dcc7-46cf-b36e-9fb40300afa3
                © 2011 American Society for Nutrition

                This is a free access article, distributed under terms ( http://www.nutrition.org/publications/guidelines-and-policies/license/) which permit unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status: a Roundtable Review

                Nutrition & Dietetics
                Nutrition & Dietetics

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