Biomarker-calibrated dietary macronutrient densities and their comparative associations with chronic disease risk in a cohort of postmenopausal females

BACKGROUND: Associations between dietary macronutrient composition and risk of major chronic diseases remain uncertain, partly because of reliance on self-reported dietary intake. OBJECTIVES: To make comparisons among biomarker-calibrated dietary macronutrient densities and risks of cardiovascular diseases (CVDs), cancers, and type-2 diabetes (T2D) over long-term follow-up in Women's Health Initiative (WHI) cohorts of postmenopausal United States females. METHODS: Biomarker-based intake estimates from serum and 24-h urine metabolomic profiles were calculated for macronutrient component densities in a WHI Nutrition and Physical Activity Assessment Study (n = 436). These values were regressed linearly on corresponding food frequency questionnaire (FFQ) density estimates and participant characteristics to produce calibration equations that adjust FFQ estimates for random and systematic measurement error. Biomarker-calibrated dietary density estimates were calculated in larger WHI cohorts (n = 82,121). Hazard ratio (HR) methods were used to prospectively relate both biomarker-calibrated intake assessments and, separately, FFQ assessments to chronic disease risk. RESULTS: criterion could be developed for protein, carbohydrate, saturated fatty acid (SFA), and polyunsaturated fatty acid (PUFA) densities, and for several specific SFA and PUFA densities, but not for monounsaturated fatty acid density. HR estimates (95% confidence intervals) for 20% increments in biomarker-calibrated SFA density and PUFA density, compared with other macronutrient sources, were 1.13 (1.04, 1.23) and 0.95 (0.87, 1.04) for coronary artery disease (CAD), 1.02 (0.96, 1.08) and 1.10 (1.02, 1.17) for breast cancer, and 1.07 (1.04, 1.11) and 1.07 (1.03, 1.12) for T2D. Protein density was also directly associated with T2D risk. Positive SFA density associations with CVD and T2D risk may be attributable to dietary palmitic acid. CONCLUSIONS: Compared with other macronutrient sources, risk may be elevated for CAD at higher SFA density, for breast cancer at higher PUFA density, and for T2D risk at higher SFA, PUFA, and protein densities, among postmenopausal United States females. This study was registered with clinicaltrials.gov identifier as NCT00000611 (https://clinicaltrials.gov/study/NCT00000611).