Low-Fat Dietary Pattern among Postmenopausal Women Influences Long-Term Cancer, Cardiovascular Disease, and Diabetes Outcomes

Abstract

Background: The preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial.

Objective: The DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered.

Methods: The DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d.

Results: Over an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin.

Conclusions: Reduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women.

This trial was registered at clinicaltrials.gov as NCT00000611.

Keywords: cancer; carbohydrate; cardiovascular disease; diabetes; health benefits and risks; low-fat dietary pattern; nutritional behavioral intervention; randomized controlled trial.

Copyright © American Society for Nutrition 2019.

Figures

FIGURE 1

Participant flow diagram for the WHI trial of a low-fat dietary pattern through extended follow-up. Participants were randomly assigned to a low-fat dietary pattern intervention or usual-diet comparison group. All participants were postmenopausal and in the age range 50–79 y when enrolled during 1993–1998 at 40 US clinical centers. DM, dietary modification; NDI, National Death Index; WHI, Women's Health Initiative.

FIGURE 2

Monitored and other important outcomes in the Women's Health Initiative Dietary Modification trial (n = 48,835) during the 8.5-y (median) intervention phase, and over cumulative follow-up of 13.4 y for adjudicated CVD outcomes and 19.6 y for other outcomes. Summary statistics and forest plots are shown for randomly assigned groups, during the (A) intervention period and (B) cumulative follow-up. HRs (95% CIs) and P values are from Cox regression models with baseline hazard stratified on age at random assignment (50–54, 55–59, 60–69, and 70–79 y), ethnicity (white, black, and other), hysterectomy status (yes or no), prior disease (if applicable), randomization status in the hormone therapy trials (CEE, CEE-placebo, CEE + MPA, CEE + MPA placebo, and not randomized), and study phase (intervention phase, extension phase I, and extension phase II; time-dependent). Time to event is measured from date of randomization. P value is for the overall influence of random assignment on outcomes based on a score (log-rank) test. Analyses for diabetes outcomes was among participants without prevalent diabetes at baseline (n = 45,595). All participants were postmenopausal and in the age range 50–79 y when enrolled during 1993–1998 at 40 US clinical centers. CEE, conjugated equine estrogens; CVD, cardiovascular disease; DM-C, dietary modification comparison group; DM-I, dietary modification intervention group; MPA, medroxyprogesterone acetate.

FIGURE 3

Monitored outcomes and other important outcomes in the Women's Health Initiative Dietary Modification trial among participants (n = 43,232) without prior CVD (3947 participants excluded based on missing hypertension status at baseline) during the 8.5-y (median) intervention phase (A, C), and over cumulative follow-up (B, D) of 13.4 y for adjudicated CVD outcomes and 19.6 y for other outcomes, stratified by baseline hypertension status (A, B: normotensive, compared with C, D: hypertensive). Summary statistics and forest plots are shown for randomly assigned groups without prior history of CVD during the intervention period (A, C), by hypertension status; likewise for cumulative follow-up (B, D). For each panel, regression models were expanded by stratifying on hypertension status (normotensive compared with hypertensive) and including an interaction term. P value is for the interaction between randomization group and hypertension status based on a score test. All participants were postmenopausal and in the age range 50–79 y when enrolled during 1993–1998 at 40 US clinical centers. CVD, cardiovascular disease; DM-C, dietary modification comparison group; DM-I, dietary modification intervention group.

FIGURE 4

Monitored and other important outcomes in the Women's Health Initiative Dietary Modification trial (n = 48,622, 213 participants excluded owing to missing BMI data at baseline) during the 8.5-y intervention (median) phase (A, C), and over cumulative follow-up (B, D) of 13.4 y for adjudicated CVD outcomes and 19.6 y for other outcomes, stratified by baseline BMI group (A, B, <30; compared with C, D, ≥30). Summary statistics and forest plots are shown for randomly assigned groups during the intervention period by BMI group; likewise for cumulative follow-up. For each panel, regression models as used for Figure 2 were expanded by stratifying on BMI group (<30 compared with ≥30) and included an interaction term between randomization assignment and BMI group, with the corresponding interaction P value based on a score test. All participants were postmenopausal and in the age range 50–79 y when enrolled during 1993–1998 at 40 US clinical centers. BMI in kg/m2. CVD, cardiovascular disease; DM-C, dietary modification comparison group; DM-I, dietary modification intervention group.