Low-Fat Dietary Pattern and Risk of Breast Cancer, Colorectal Cancer, and Cardiovascular Disease: The Women’s Health Initiative (WHI) Randomized Controlled Dietary Modification Trial

February 2006

Findings Summary

Description and Overview
Beginning in 1993, the Women’s Health Initiative enrolled 48,835 women aged 50-79 in the WHI Dietary Study (also referred to as the Dietary Modification Trial). The Dietary Study researched the effect of a low-fat (20% of calories), and high fruit, vegetable, and grain diet on breast cancer, colorectal cancer, and heart disease in postmenopausal women. Women were randomized (assigned by chance) to either a Dietary Change (intervention) group or a Comparison group, making this the largest randomized clinical trial of low-fat diet ever conducted.
For the Dietary Change group, goals were to follow a low-fat dietary pattern, reducing fat intake and increasing intake of fruits, vegetables, and grains. The Comparison group followed their usual diet. The low-fat dietary pattern was not designed for weight loss and women were not asked to lose weight. Dietary Study participants were followed for an average of 8.1 years, attending annual clinic visits and completing health forms. During the course of the study, Dietary Change women attended periodic group sessions with a clinic nutritionist to learn how to follow the low-fat dietary pattern.
Starting from an average of about 35% energy from fat at the time they joined the study, women in the Dietary Change group reduced their fat intake to 24% of total calories by the end of the first year. By the end of the study, their average intake was 29% energy from fat. Women in the Comparison group stayed at about the same level of fat intake throughout the study. The difference in fat intake between the Dietary Change and Comparison groups declined over time, from 11% at year one to 8% at the end of the study. Women in the Dietary Change group also increased their fruit/vegetable intake, but had a more challenging time with increasing grains.
Breast Cancer Findings
The Dietary Study ended in March 2005 after an average of 8.1 years of follow-up. During that time, there were a total of 1,727 cases of invasive breast cancer in Dietary Study participants. Breast cancer rates were 9% lower in women in the Dietary Change group compared to women in the Comparison group. This means that out of 10,000 women, 42 in the Dietary Change group and 45 in the Comparison group, on average, developed breast cancer each year. However, this difference between groups in breast cancer risk was not quite statistically significant. A difference of this size or larger could occur by chance alone, with a probability of about 7%, whereas scientists prefer the probability to be 5% or less to be considered statistically significant.
Additional analyses support the trend toward a lower risk of breast cancer among women in the Dietary Change group. Dietary Change group women who had higher levels of fat intake at the start of the study made larger reductions in fat intake than did the Dietary Change group as a whole, and had a greater reduction in breast cancer risk than did those with a lower fat intake. Also, breast cancer risk differed according to whether the breast tumor cells had receptors for estrogen or progesterone. The low-fat diet reduced blood estradiol (estrogen) levels by 15%. Estrogen is thought to be a risk factor for breast cancer.
Possible reasons the overall difference in breast cancer risk between the Dietary Change and Comparison groups was not statistically significant include:
  • Insufficient follow-up time. Longer follow-up may be needed to see a significant reduction in breast cancer. Because diet can have lasting effects, the continued follow-up of Dietary Study women in the WHI Extension Study is expected to provide the information needed for a more conclusive test of the low-fat dietary pattern.
  • Dietary fat intake not low enough. Greater reductions in fat intake may be needed to achieve a significant effect. Dietary Change group participants did not lower their fat intake to the extent that scientists had hoped they would. It is possible that a lower intake than participants were able to achieve would be needed to see a significant effect on breast cancer risk.
The current findings from the WHI Dietary Study are not clear enough to recommend a lower fat intake for most women to prevent breast cancer, but women who are eating a high fat diet may benefit by reducing fat intake. Women should continue to take steps to reduce their risk of invasive breast cancer, such as having regular mammograms and breast examinations.
Colorectal Cancer Findings
Results from the WHI Dietary Study showed that the low-fat dietary pattern did not reduce the risk of colorectal cancer. In Dietary Study participants, there were 480 cases of colorectal cancer, with similar rates in the Dietary Change (on average, 13 per 10,000 women per year) and Comparison (12 per 10,000 women per year) groups. The 8% difference (increase) in risk was not close to being statistically significant. The results were similar when looking at where the cancer occurred – the entire colon, upper or lower colon, or rectum. The number of women reporting polyps was 9% lower (significant) in the Dietary Change group (on average, 216 per 10,000 per year) than the Comparison group (235 per 10,000 per year).
Women who closely followed the low-fat dietary pattern were not found to have more benefit than those who did not, nor did women who had started with higher fat intakes at the beginning of the study show greater benefit. The data did suggest a possible reduction in colorectal cancer risk in Dietary Change women who were either taking aspirin or were on combination estrogen plus progestin hormone therapy; however, these findings may have occurred by chance.
Overall, these results suggest that a low-fat dietary pattern, with increased fruits, vegetables, and grains, is not likely to prevent colorectal cancer in postmenopausal women followed for 8 years. The reduction in polyps suggests that a benefit for colorectal cancer risk might be found when women are followed for a longer period of time.
Cardiovascular Disease (Heart attack and Stroke) Findings
To study the effect of the WHI low-fat dietary pattern on heart disease, researchers looked at how many participants had coronary heart disease (heart attack or death from heart disease). They found that the low-fat dietary pattern did not reduce the risk of heart disease, although the intervention was not designed specifically to reduce heart disease. In WHI Dietary Study participants, there were 1422 cases of coronary heart disease, with similar rates in the Dietary Change (on average, 35 per 10,000 women per year) and the Comparison (on average, 36 per 10,000 women per year) groups. The 2% difference (decrease) in risk of coronary heart disease was not statistically significant. When women who had a history of heart disease when they joined the study were removed from the analyses, there was a 7% reduction in heart disease, but this was not statistically significant. There was also no statistically significant effect on stroke.
There were, however, small favorable effects of the low-fat dietary pattern on some risk factors. There were small but significant improvements in body weight, low-density lipoprotein (LDL) cholesterol, diastolic blood pressure, and Factor VII C (a blood clotting factor).
One important finding from the Dietary Study is that a low-fat, high carbohydrate diet does not necessarily increase body weight, blood triglycerides, or indicators of increased risk of diabetes such as blood glucose or insulin levels.
There was no greater effect of the intervention on heart disease in women who participated in most of the study activities, or in women who started with higher fat intakes. Those who reached the lowest levels of saturated fat or trans fat and the highest level of fruits and vegetables had greater reductions in low-density lipoprotein (LDL) cholesterol and heart disease. However, because these analyses involved smaller groups of women, the findings are not as reliable as those which include the entire group.
The most likely explanation for the lack of a statistically significant effect on heart disease is that the dietary pattern reduced all types of fat, in order to test whether reduction in total fat prevents breast cancer. It was anticipated that reducing total fat would also lead to reductions in saturated fat with a consequent lowering of blood cholesterol. The lowering of blood cholesterol in Dietary Change participants was less than anticipated, and therefore there was no effect on heart disease. A diet designed to reduce risk of heart disease would focus specifically on reducing saturated and trans fats, and would not reduce polyunsaturated and monounsaturated fats. Studies have shown that such a diet leads to lower blood cholesterol and reduces the risk of heart disease.
A low-fat dietary pattern is consistent with current national dietary guidelines and remains an option for generally healthy postmenopausal women. The Dietary Guidelines for Americans 2005 remain a healthy option for prevention of heart disease, especially when accompanied by physical activity and weight management. These guidelines include a mainly plant-based diet rich in vegetables, fruit, whole grains, nuts, beans, low-fat dairy products, and fish. The guidelines suggest consuming 20-35% energy from fat, with reductions in saturated and trans fats, and most fats coming from polyunsaturated and monounsaturated sources, such as vegetables and nuts. The guidelines also recommend five to nine one-half-cup servings of fruits and vegetables and three or more servings of whole grains daily. To link to the current guidelines, go to www.healthierus.gov/dietaryguidelines.
A low fat dietary pattern may have some potential for reducing breast cancer risk, particularly in women consuming a high fat diet. However, the current findings are not strong enough to make a recommendation that most women should focus on low-fat dietary patterns to prevent breast cancer. These findings indicate that a low-fat diet provided no protection from colorectal cancer and should not be recommended for that purpose. The low-fat diet did not specifically focus on reducing saturated fat, had only a small effect on blood cholesterol, and did not reduce the risk of heart disease. However, the WHI results suggest that women who achieved greater reductions in saturated fat or trans fat, and higher intakes of fruits and vegetables, might experience a reduced risk of heart attacks. Overall, the WHI low fat dietary pattern is not inconsistent with the USDA Dietary Guidelines for Americans 2005 and remains a healthy option for postmenopausal women in general.