Abstract Background: Advanced glycation end-products (AGEs) are compounds produced in the body during the metabolism of protein, lipids or nucleic acids, and have been implicated in breast cancer risk and prognosis. In the Women’s Health Initiative (WHI) Dietary Modification (DM) randomized trial, the low-fat dietary intervention significantly reduced breast cancer mortality (P = 0.02) over 20 years of follow up. As dietary AGEs (dAGEs) are associated with westernized diets and adversely impact breast cancer prognosis, we examined whether the WHI low-fat dietary pattern influenced consumption of dAGEs. Methods: A total of 48,835 postmenopausal women, ages 50 to 79, were randomized to a low-fat dietary intervention (n = 19,541) versus usual diet comparison (n=29,294). Food frequency questionnaires were administered at baseline, year 1, and yearly thereafter from a rotating subgroup and were used to estimate dAGE scores (kilo Units/100 kilocalories kU/1000 kcal) using a commonly referenced database. Multivariate regressions with repeated measures for dAGEs were examined by DM randomization group and follow-up duration (baseline, years 1, 2-4 and 5-7). Results: Baseline mean dAGE scores were similar for intervention (7,542 kU/1000 kcal, SD = 912) and comparison (7,514 kU/1000 kcal, SD=917) groups. In multivariate regression, the largest difference in dAGE was observed after 1-year follow-up (intervention: 5,362 kU/1000 kcal versus comparison: 7,159 kU/1000 kcal). Subsequently, persistently lower dAGE levels were found in the intervention versus comparison group, with some attenuation of the difference: visit years 2-4 (intervention: 5,818 kU/1000 kcal v. comparison: 7,458 kU/1000 kcal) and visit years 5-7 (intervention: 6,236 kU/1000 kcal v. comparison: 7,669 kU/1000 kcal; P 0.0001). Conclusions: Among postmenopausal women, a low-fat dietary intervention substantially reduced dAGE intake. Future studies will explore whether reduced dAGE intake moderated the favorable breast cancer outcomes previously reported in the WHI DM trial. Citation Format: M. S. Pichardo, R. P. Hunt, L. L. Peterson, K. Pan, M. Coday, S. Jung, L. Snetselaar, M. L. Neuhouser, S. E. Steck, F. K. Tabung, N. Saquib, J. E. Manson, R. T. Chlebowski. The Role of a Low-Fat Dietary Intervention on Intake of Dietary Advanced Glycation End Products in Postmenopausal Women abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-02.
Pichardo et al. (Tue,) studied this question.