The Women’s Health Initiative: Implications for clinicians
ABSTRACTThe Women’s Health Initiative (WHI), the largest and longest randomized controlled study to date of the effect of dietary change on disease outcomes in postmenopausal women, failed to show that a low-fat diet prevents breast cancer, colon cancer, or cardiovascular disease. However, as the authors point out, the WHI Extension Study provides opportunities to assess whether nearly significant differences in breast cancer rates at 8 years become significant after 10 years of follow-up.
KEY POINTS
- Colon cancer rates did not differ between the dietary intervention group and the comparison group, but the number of polyps and adenomas reported was significantly lower in the dietary intervention group.
- Risk factors for coronary heart disease improved slightly with the diet, but by trial year 3, differences in overall rates of coronary heart disease and stroke in the two groups were not statistically significant.
- When stratified by quartiles, those who reduced their intake of saturated and trans-fatty acids the most, or who increased their intake of fruits and vegetables the most, appeared to have a moderate reduction in the risk of coronary heart disease.
HOW OUTCOMES WERE ASSESSED
The primary assessments of clinical outcome1–3 were mammographic screening, a self-reported medical history documented by a review of medical records, and electrocardiograms digitally obtained every 3 years. Mammograms and electrocardiograms were centrally adjudicated. The diagnosis of acute myocardial infarction was based on an algorithm that included cardiac pain, enzyme levels, and electrocardiographic readings.
OVERALL RESULTS
At 8.1 years, the incidence of breast cancer was 9% lower in the intervention group than in the comparison group (95% confidence interval [CI] = 0.83–1.01; P = .07, P = .09 weighted for length of follow-up).3 Subgroup analysis further showed that women who reported higher intakes of total dietary fat at baseline reduced their risk of breast cancer by 22% (95% CI = 0.64–0.96). Whether extended follow-up will show a significant association has yet to be determined.
Colon cancer rates did not differ between groups, but the number of polyps and adenomas reported was significantly lower in the dietary intervention group.1 The rate of colon cancer will also be included in the extended follow-up study of the WHI.
Risk factors for coronary heart disease in both groups—including levels of serum total cholesterol and serum low-density lipoprotein cholesterol, body weight, body mass index, diastolic blood pressure, and factor VIIc—improved slightly, but at year 3 of the trial, differences in overall rates of coronary heart disease and stroke in the two groups were not statistically significant.2 In addition, the low-fat diet intervention was associated with a reduction in blood estradiol concentrations between baseline and year 1.3 At the end of the study, however, differences in rates of breast cancer, colorectal cancer, and heart disease between the two groups were not statistically significant.
RESULTS OF DIETARY MODIFICATIONS
Fat as a percentage of total calories
At the beginning of the WHI, all participants reported consuming an average of 35% of their caloric intake from fat (Table 1). At 1 year from baseline, the fat intake decreased to 24.3% in the intervention group (short of the study goal of 20%); this level had risen again to 26.7% by year 3 and to 28.8% at the end of the study. Stratified by quartile, women who achieved the greatest reductions in saturated and trans-fatty acids or the largest increases in their intake of fruits and vegetables appeared to have a moderate reduction in the risk of coronary heart disease.2 Women in the comparison group also decreased their fat intake initially, but to a lesser degree, and gradually increased it again thereafter. The mean net difference in self-reported total fat intake between the intervention group and the comparison group at 6 years was 8.2% (P < .001) (study goal, 13%).1–3
Intake of fruits, vegetables, and grains
At baseline, fruit and vegetable intake averaged 3.6 servings per day (Table 1). In the intervention group, this increased to 5.1 servings per day at year 1, and to 5.2 servings at year 3, but at the end of the study it had decreased to 4.9 servings.
Women in the intervention group were eating 4.7 servings of grains per day at baseline. This increased to 5.1 servings at year 1 and then decreased to 4.6 servings at year 3 and to 4.3 servings at the end of the study. It seems that as the women grew older their determination to increase servings of these foods diminished.
Proponents of some currently popular diets blame weight gain on a higher intake of carbohydrates, but the women following the WHI low-fat diet did not gain weight.2
Total fat vs saturated fat
Intake of total fat and saturated fat decreased in the intervention group during the study, but the difference between fat intake in the intervention group and that in the comparison group did not reach the degree expected.
At year 1, total fat as a percentage of total caloric intake was 10.8 percentage points below that of the comparison group, whereas the study expected difference was 13.0. At the end of the trial, the difference was only 8.2 percentage points, whereas the expected difference was 11.0.
Intake of all fatty acids (saturated and unsaturated) decreased at year 1, but then went back up slightly by the end of the trial but did not exceed baseline levels, and saturated fatty acids remained well below baseline levels: 9.5% vs 12.5% of caloric intake at baseline.4
