Application of blood concentration biomarkers in nutritional epidemiology: Example of carotenoid and tocopherol intake in relation to chronic disease risk

Ross L. Prentice, Mary Pettinger, Marian L. Neuhouser, Lesley F. Tinker, Ying Huang, Cheng Zheng, Jo Ann E. Manson, Yasmin Mossavar-Rahmani, Garnet L. Anderson, Johanna W. Lampe

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background: Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. Objective: The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. Methods: Serum concentrations of a-and β-carotene, lutein plus zeaxanthin (L + Z), and a-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. Results: HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of a-and β-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of a-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. Conclusions: Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on selfreported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at as NCT00000611.

Original languageEnglish (US)
Pages (from-to)1189-1196
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Issue number4
StatePublished - Apr 1 2019
Externally publishedYes


  • Biomarker
  • Cancer
  • Cardiovascular disease
  • Carotenoid
  • Diabetes
  • Diet
  • Measurement error
  • Tocopherol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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