Biomarker-assessed total energy intake and its cohort study association with all-cause mortality in postmenopausal females

Background: The association of total energy intake (EI) with all-cause mortality is uncertain as are the dependencies of this association on age and weight change history. Objectives: To identify an EI biomarker suitable for use in epidemiologic association studies and to study EI associations with total mortality in a Women's Health Initiative (WHI) cohort of postmenopausal United States females (1993–present). Methods: EI biomarkers were developed based on doubly labeled water (DLW) total energy expenditure (TEE) and weight variation during the 2-wk DLW protocol period using the energy balance method in an embedded feeding study (n = 153). This along with 2 earlier WHI nutrition biomarker studies having TEE assessments (n = 1131 total), with 14.6 y (median) follow-up, constituted a prospective cohort for the study of EI and all-cause mortality. Results: An empirical biomarker for log(EI) was developed that had a correlation of 0.73 with log(feeding study-consumed EI). The overall association between EI and mortality was nonsignificant. The association, however, depended on age (P = 0.009), with lower EI associated with lower mortality at younger ages, and also on preceding weight change history (P = 0.03). Among participants with stable or increasing weight, mortality hazard ratios (95% confidence intervals [CIs]) for a 12% lower EI were 0.66 (95% CI: 0.51, 0.87) at age 60, 0.84 (95% CI: 0.72, 0.98) at age 70, and 1.06 (95% CI: 0.87, 1.29) at age 80. Corresponding values for participants having preceding weight loss were 0.83 (95% CI: 0.61, 1.12) at age 60, 1.05 (95% CI: 0.87, 1.26) at age 70, and 1.33 (95% CI: 1.08, 1.63) at age 80. A previously considered EI biomarker, using a theoretical model for variation in body fat and fat-free mass components over time, gave similar results following rescaling. Conclusions: Lower EI is associated with lower all-cause mortality among younger postmenopausal females with stable or increasing weight and with higher mortality among older females with weight loss. This study was registered with clinicaltrials.gov as NCT00000611.