Measurement of Vitamin D for Epidemiologic and Clinical Research: Shining Light on a Complex Decision

Anne Marie Z. Jukic, Andrew N. Hoofnagle, Pamela L Lutsey

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Vitamin D is a fat-soluble vitamin that is synthesized in the skin with exposure to sunlight or is ingested from dietary supplements or food. There has been a dramatic increase in research on vitamin D, linking it with health outcomes as varied as reproductive function, infection, cardiovascular disease, and cancer. The study of vitamin D has generated much excitement, partly because there is an ideal intervention: Low levels may be common and can be remedied with widely available supplements. Determination of vitamin D status is complex and has advanced dramatically in the past 5 years. In this paper, we begin by describing important considerations for measurement of total 25-hydroxyvitamin D (25(OH)D), the biomarker traditionally assessed in epidemiologic studies. While 25(OH)D remains the most commonly measured biomarker, emerging evidence suggests that other related analytes may contribute to the characterization of an individual's vitamin D status (e.g., vitamin D-binding protein, bioavailable and free 25(OH)D, the C-3 epimer of 25(OH)D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D). The measurement of these analytes is also complex, and there are important considerations for deciding whether their measurement is warranted in new research studies. Herein we discuss these issues and provide the reader with an up-to-date synthesis of research on vitamin D measurement options and considerations.

Original languageEnglish (US)
Pages (from-to)879-890
Number of pages12
JournalAmerican journal of epidemiology
Issue number4
StatePublished - Apr 1 2018

Bibliographical note

Funding Information:
Author affiliations: Department of Chronic Disease Epidemiology, Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut (Anne Marie Z. Jukic); Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington (Andrew N. Hoofnagle); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota (Pamela L. Lutsey). This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (award R00HD079659) and by the National Institute on Aging (grant (R01AG041776), the National Heart, Lung, and Blood Institute (grant R01HL103706), and the Office of Dietary Supplements, National Institutes of Health (grant R01HL103706-S1). We thank Gabriela Leskur for her contributions to the design of Figure 1. The University of Washington (A.N.H.) receives grant funding from Waters Corporation (Milford, Massachusetts), a manufacturer of mass spectrometry equipment.


  • 25-hydroxyvitamin D
  • Vitamin D
  • biomarkers
  • epimers
  • immunoassays
  • mass spectrometry
  • validity

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