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 the risk of major chronic diseases remain uncertain, partly due to reliance on self-reported dietary intake. OBJECTIVES We make comparisons among biomarker-calibrated dietary macronutrient densities and the 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 U.S. females. METHODS Biomarker-based intake estimates from serum and 24-hour 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 FFQ density estimates and participant characteristics to produce calibration equations that adjust food frequency questionnaire (FFQ) estimates for random and systematic measurement error. Biomarker-calibrated dietary density estimates were calculated in larger WHI cohorts (n=82,121). Hazard ratio methods were used to prospectively relate both biomarker-calibrated intake assessments and, separately, FFQ assessments to chronic disease risk. RESULTS Calibration equations meeting an adjusted R2 criterion could be developed for protein, carbohydrate, saturated (SFA) and polyunsaturated (PUFA) fatty acid densities, and for several specific SFA and PUFA densities, but not for monounsaturated fatty acid density. Hazard ratio (HR) estimates (95% CIs) for 20% increments in biomarker-calibrated SFA density and PUFA density, compared to other macronutrient sources, were respectively 1.13 (1.04, 1.23) and 0.95 (0.87, 1.04) for coronary heart disease (CHD), 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 also was directly associated with T2D risk. Positive SFA density associations with CVD and T2D risk may be attributable to dietary palmitic acid. CONCLUSIONS Compared to other macronutrient sources, risk may be elevated for CHD at higher SFA density, for breast cancer at higher PUFA density, and for T2D risk at higher SFA, PUFA, and protein densities, among postmenopausal U.S. females. This study is registered with clinicaltrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.