Low-Fat Dietary Pattern and Health Outcomes in the Women's Health Initiative Randomized Clinical Trial

Abstract

Background: Debate, stimulated recently by the Prospective Urban Rural Epidemiology study, concerns the preferred macronutrient dietary composition. Here we provide a comprehensive overview of health outcomes in the Women's Health Initiative Dietary Modification (DM) trial. Methods: The DM trial was a randomized, controlled trial conducted at 40 centres in the USA. 48,835 postmenopausal women, aged 50-79 years, with baseline intake of ≥32% energy from fat were randomly assigned by a computerized, stratified, permuted block algorithm to a low-fat dietary pattern intervention group (40%) or to a usual diet comparison group (60%) during 1993-8. Intervention goals were to reduce fat intake to 20% of total energy and increase vegetables, fruit, and grains. Invasive breast cancer and colorectal cancer were co-primary outcomes, and coronary heart disease was secondary, with other health outcomes also monitored. Findings: After the 8.5-year (mean) intervention period, intervention versus comparison group differences included lower fat by 8-10% of total energy and higher carbohydrate by 8-10% of total energy with increases in vegetables, fruit, and grains. Intervention and comparison group annual incidences were 0.42 and 0.46 (hazard ratio 0.92, 95% CI - 0.84 to 1.01) for invasive breast cancer, and 0.13 and 0.12 (HR, 1.07, 95% CI - 0.92 to 1.27) for colorectal cancer, with overall unchanged CHD incidence and total mortality. During 17.7-years (mean) cumulative follow-up, statistically significant reduction in deaths following breast cancer, diabetes requiring insulin, and CHD among women who were not hypertensive, emerged in intervention group, primarily among participants who were obese at enrollment. Interpretation: In postmenopausal women, reduction in total dietary fat with commensurate increase in carbohydrate did not increase all-cause mortality or have adverse health consequences, while having some health benefits. Clinical Trial Number: This study is registered with clinicaltrials.gov identifier: NC0611. Funding Statement: The development of this paper is partially supported by National Cancer Institute grants R01 CA119171 and R01 CA10921. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C, and these sources also partially support the development of this paper. Declaration of Interests: None of the authors report a conflict of interest related to this study. Ethics Approval Statement: Institutional review board approval was obtained at each individual center, and all participants provided written informed consent.