Nutritional epidemiology and the Women's Health Initiative: A review

Ross L. Prentice, Barbara V. Howard, Linda Van Horn, Marian L. Neuhouser, Garnet L. Anderson, Lesley F. Tinker, Johanna W. Lampe, Daniel Raftery, Mary Pettinger, Aaron K. Aragaki, Cynthia A. Thomson, Yasmin Mossavar-Rahmani, Marcia L. Stefanick, Jane A. Cauley, Jacques E. Rossouw, Jo Ann E. Manson, Rowan T. Chlebowski

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50-79 y when enrolled during 1993-1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007-2009) and a related controlled feeding study among 153 WHI participants (2010-2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. This trial was registered at as NCT00000611.

Original languageEnglish (US)
Pages (from-to)1083-1092
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Issue number5
StatePublished - May 1 2021


  • biomarker
  • cancer
  • cardiovascular disease
  • diabetes
  • diet assessment
  • dietary intervention
  • energy consumption
  • macronutrient
  • measurement error
  • women's health

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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