Variability and Reproducibility of Circulating Vitamin D in a Nationwide U.S. Population

Divisions of Cancer Epidemiology and Genetics (J.M.M., B.I.G., M.S.L., D.M.F.) and Cancer Prevention (K.W.D.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20852
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 11/2012; 98(1). DOI: 10.1210/jc.2012-2643
Source: PubMed


Context:Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time.Objective:This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U.S. radiologic technologists.Design and Participants:We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined.Results:The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%.Conclusion:Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations.

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    • "The risk of bias associated with exposure measurement was common to the three studies. Indeed, and as detailed in Table 2, vitamin D was measured once, between 5–8 years depending on the study, before the assessment of the outcomes, thus limiting the reliability of the value obtained as a reflection of integrated vitamin D nutritional status over the follow-up time [30]. In addition, the methods of handling the samples (e.g., thawing procedure) may have affected the accuracy of the results. "
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    ABSTRACT: Background There is conflicting evidence about the association between low vitamin D levels in children and development of asthma in later life. The objective of this study was to systematically review the evidence for an epidemiological association between low serum levels of vitamin D and the diagnosis of asthma in children. Methods We used the Cochrane methodology for conducting systematic reviews. The search strategy included an electronic search of MEDLINE and EMBASE in February 2013. Two reviewers completed, in duplicate and independently, study selection, data abstraction, and assessment of risk of bias. Results Of 1081 identified citations, three cohort studies met eligibility criteria. Two studies found that low serum vitamin D level is associated with an increased risk of developing asthma late in childhood, while the third study found no association with either vitamin D2 or vitamin D3 levels. All three studies suffer from major methodological shortcomings that limit our confidence in their results. Conclusions Available epidemiological evidence suggests a potential association between low serum levels of vitamin D and the diagnosis of asthma in children. High quality studies are needed to reliably answer the question of interest.
    Full-text · Article · Jun 2014 · Allergy Asthma and Clinical Immunology
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    ABSTRACT: Prospective analyses have yet to uncover a consistent relationship between vitamin D status and incidence and mortality of rarer cancers including esophageal and upper gastrointestinal cancers. We searched PubMed for literature regarding the epidemiology of upper gastrointestinal cancers and vitamin D published over the last decade and then summarized and critiqued the results of these studies in this review. The search yielded nine relevant studies. Overall, no consistent relationship was reported between serum vitamin D levels or a surrogate and upper gastrointestinal cancers. Four studies reported negative correlations between vitamin D status and upper gastrointestinal cancer, three reported positive correlations, one reported no correlation, and one reported both positive and negative correlations. No relationship has been established based on epidemiological data, but studies examining sun exposure consistently report an inverse association with esophageal cancer. The current literature is limited by the methods used to assess vitamin D status, lack of specific data for the types of upper gastrointestinal cancer, and failure to establish a temporal relationship between vitamin D status assessment and presentation of upper gastrointestinal cancer. It is possible that the lack of a consistent relationship is a consequence of inaccurate and imprecise assessment of vitamin D status.
    Preview · Article · Apr 2013 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: BACKGROUND: The seasonal variation in circulating 25-hydroxyvitamin D [25(OH)D] concentrations is large relative to mean values. Single measurements may misclassify annual exposure, which may lead to bias in research and complicate clinical decision making. OBJECTIVE: We aimed to develop and validate a model for adjusting a single measurement of a serum 25(OH)D concentration to the time of year it was measured. DESIGN: We measured serum 25(OH)D concentrations by using mass spectrometry in 6476 participants from the Multi-Ethnic Study of Atherosclerosis at baseline and again in a subset of 368 participants at a median of 17 mo later. We estimated a cosinor model to describe the seasonal variability in 25(OH)D concentrations and evaluated this model by using follow-up 25(OH)D measurements. RESULTS: The mean age of subjects was 62.1 y, 61.2% of participants were nonwhite, and 53.3% of participants were women. The cosinor model predicted follow-up 25(OH)D concentrations better than a single measurement [difference in root mean squared error (RMSE): 1.3 ng/mL; P< 0.001]. The cosinor model also better predicted the measured annual mean 25(OH)D concentration (difference in RMSE: 1.0 ng/mL; P< 0.001). Annual mean 25(OH)D concentrations estimated from the cosinor model reclassified 7.1% of participants with regard to 25(OH)D deficiency, which was defined as <20 ng/mL. An estimated annual mean 25(OH)D concentration <20 ng/mL was significantly associated with lower bone mineral density, whereas an untransformed 25(OH)D concentration <20 ng/mL was not. CONCLUSIONS: Cross-sectional data can be used to estimate subject-specific mean annual 25(OH)D concentrations from single values by using a cosinor model. The tool we developed by using this approach may assist research and clinical care of adults in North America by reducing the misclassification of 25(OH)D deficiency.
    Preview · Article · Apr 2013 · American Journal of Clinical Nutrition
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