OUP accepted manuscript

The associations of red and processed meat with chronic disease risk remains unsettled, in part because of measurement error in self-reported diet.To develop metabolomics-based biomarkers for red and processed meat, and to associate biomarker-calibrated meat intake with chronic disease risk among postmenopausal women.Women's Health Initiative (WHI) cohorts were utilized. Participants were postmenopausal women aged 50-79 y when enrolled at 40 US clinical centers during 1993-1998, with embedded human feeding and nutrition biomarker studies. Literature reports of metabolomics correlates of meat consumption were used to develop meat intake biomarkers from serum and 24-hour urine metabolites in a 153-participant feeding study (2010-2014). Resulting biomarkers were used in a 450-participant biomarker study (2007-2009) to develop linear regression calibration equations that adjust food frequency questionnaire intakes for random and systematic measurement error. Biomarker-calibrated meat intakes were associated with cardiovascular disease, cancer, and diabetes incidence among 81,954 WHI participants (1993-2020).Biomarkers and calibration equations meeting pre-specified criteria were developed for red meat and red plus processed meat consumption combined, but not for processed meat. Following control for non-dietary confounding factors calibrated red meat hazard ratios (95% CIs) for a 40% increment above the median intake were 1.10 (1.07, 1.14) for coronary heart disease, 1.26 (1.20, 1.33) for heart failure, 1.10 (1.07, 1.13) for breast cancer, 1.07 (1.05, 1.09) for total invasive cancer, and 1.37 (1.34, 1.39) for diabetes. Hazard ratios for red plus processed meat intake were similar. Hazard ratios were close to the null, and mostly non-significant following additional control for dietary potential confounding factors, including calibrated total energy consumption.A relatively high meat dietary pattern is associated with somewhat higher chronic disease risks. These elevations appear to be largely attributable to the dietary pattern, rather than to consumption of red or processed meat per se.