SEATTLE — Feb. 7, 2006 — Adopting a low-fat diet in later life and following such a regimen for nearly a decade does not appear to have a significant impact on reducing the overall risk of breast cancer, colorectal cancer or heart disease, according to a Women's Health Initiative study that involved nearly 50,000 postmenopausal women across the United States. The results of the federally funded dietary modification study will be published in a series of three papers — two with lead authors at Fred Hutchinson Cancer Research Center and all three involving co-authors from the Hutchinson Center — in the Feb. 8 issue of the Journal of the American Medical Association, or JAMA.
The study — the first attempt to test the health impact of a low-fat diet in a randomized, controlled trial, considered the gold standard of clinical and public-health study design — did, however, uncover some encouraging trends, according to Hutchinson Center biostatistician Ross L. Prentice, Ph.D., lead author of the JAMA paper that describes the impact of a low-fat diet on breast-cancer risk, one of the primary goals of the study.
"Women in the low-fat-diet group reduced their overall rate of breast cancer by about 9 percent as compared to the women who didn't change their eating patterns, but that difference was not statistically significant; it could have been due to chance. So at this point we're not able to say with certainty that a low-fat diet reduces the risk of breast cancer," said Prentice, member and former director of the Hutchinson Center's Public Health Sciences Division. A 9 percent reduction in breast-cancer incidence means that, out of 10,000 women, 42 in the low-fat-diet group and 45 in the comparison group developed breast cancer each year.
Prentice and colleagues did find, however, that a low-fat diet was associated with a statistically significant 15 percent reduction in estradiol, a form of blood estrogen that increases the risk of breast cancer.
Women in the low-fat group also experienced a 30 percent risk reduction for a certain subtype of breast cancer: tumors that were progesterone-receptor negative. "This finding provides an interesting hypothesis for further development and reinforces that breast cancer is multifaceted; it is not a single disease," Prentice said. PR-negative tumors, while relatively rare, are difficult to treat and associated with a higher mortality rate because they are unresponsive to hormone-blocking drugs such as tamoxifen.
Significant results were seen also among women in the low-fat-diet group who began the study with the highest baseline fat consumption and among women who most strictly adhered to the study's dietary-fat goals. Women in these categories experienced a 15 percent to 20 percent overall reduction in breast-cancer incidence.
"The bottom line is that changing to a low-fat diet may reduce breast-cancer risk, especially among women who have a relatively high-fat diet to begin with, but we don't view our data as strong enough at this time to make a broad recommendation that all women initiate a low-fat diet for that purpose," Prentice said. "Additional follow up with these women may yield a stronger, statistically significant conclusion."
With regard to colorectal cancer, the study did not reveal a reduction of cancer incidence overall, but it did show a modest 9 percent decrease in self-reported colon polyps — a precursor to colon cancer — among the women in the low-fat intervention group, according to Shirley A.A. Beresford, Ph.D., lead author of the paper describing the colorectal-cancer findings.
"It is important to remember that cancers often take decades to develop, and we may only be seeing the early stages of the impact of a low-fat diet intervention on the risk of colorectal cancer and other diseases," said Beresford, a member of the Hutchinson Center's Public Health Sciences Division and a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. "The reduction in polyps suggests a possible reduction in colorectal-cancer risk could emerge over a longer time period."
No significant reduction in heart disease emerged among the women in the low-fat intervention group, who achieved only a 2.4 percent reduction in low-density lipoprotein, or LDL, the so-called "bad" cholesterol, and a 3 percent lower rate of heart disease.
The study did, however, find trends toward reduction in heart-disease risk among the subset of women in the low-fat-diet group who made the greatest reduction in consumption of saturated fat and trans fat, both of which can raise the risk of heart disease because they increase production of LDL cholesterol.
"For heart-disease prevention, the data suggests that a greater emphasis on reduction of saturated and trans fats will be needed to have a major difference," Prentice said. Barbara V. Howard, Ph.D., president of MedStar Research Institute/Howard University in Washington, D.C., was the lead author of the heart-disease paper.
Nationally, 48,835 women between the ages of 50 and 79 participated in the study, including more than 1,000 from the Seattle area. Forty percent of the women were randomly assigned to follow a low-fat diet while 60 percent of the women served as a comparison group and thus maintained their usual eating habits. The women in both groups were followed for eight years.
Those in the low-fat group aimed to consume no more than 20 percent of daily calories from fat, and to eat at least five servings of vegetables and fruits and six or more servings of grains daily. To help reach this goal, the women met regularly in small groups with nutritionists to learn how to modify their behaviors to achieve and maintain this dietary change.
At the beginning of the study, the women's baseline fat consumption was between 35 percent and 38 percent of their daily calories. A year into the study, the women in the low-fat group got 24 percent of their energy from fat — 11 percent fewer calories from fat as compared to the women who ate their usual diet — and they maintained much of that difference throughout the study.
"This was a long-term, demanding study for the women in the low-fat group, and they did a marvelous job of trying to adhere to stringent dietary goals," Prentice said. "In spite of their efforts, we achieved only 70 percent of the difference in dietary habits between the two groups that we needed to get. If we'd achieved an even higher adherence rate, I believe the study's results would have been more dramatic," Prentice said.
"While the study didn't give us the results that some people were hoping for, it suggests that we're on the right track," he said. "Women can be confident that cutting back on fat and following the recommended Dietary Guidelines for Americans certainly won't hurt when it comes to maintaining a healthy lifestyle and preventing chronic disease."
Importantly, the low-fat, high-carbohydrate diet did not increase the risk of obesity, metabolic syndrome or diabetes.
Although the intervention phase of the study is complete, five years of data collection and follow-up are planned as well. "Additional follow-up with these women may yield a stronger, statistically significant conclusion," Prentice said. "The low-fat story is partly in, but it is not over yet."
The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study, which involved researchers from dozens of institutions nationwide. Co-authors from the Hutchinson Center included Garnet L. Anderson, Ph.D.; Andrea Z. LaCroix, Ph.D.; Lesley F. Tinker, Ph.D.; Maureen M. Henderson, M.D.; Ruth L. Patterson, Ph.D.; and Deborah Bowen, Ph.D.; all current or former faculty members in the Center's Public Health Sciences Division.
The Women's Health Initiative, the largest study ever devoted to women's health, is a 15-year, multimillion-dollar study involving more than 161,000 women nationwide. The study focuses on strategies for preventing heart disease, breast and colorectal cancer, and fracture in postmenopausal women. These diseases are the major causes of death and disability in older women.
The WHI has two components: a set of randomized clinical trials and an observational study. The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer. The observational study seeks to examine the effects of lifestyle, health and risk factors on specific disease outcomes.
Initial clinical-trial results include finding that combination hormone-replacement therapy offers no overall benefit and increases the risk of breast cancer and heart disease, stroke and pulmonary embolism. Later this month, the WHI will complete its original mission with the publication of results regarding the health effects of calcium and vitamin D supplementation.
The Hutchinson Center's Public Health Sciences Division houses the WHI Clinical Coordinating Center, which oversees the statistical, epidemiologic, nutritional and clinical aspects of the study and is responsible for data collection, management and analysis. Ross L. Prentice, Ph.D., serves as principal investigator of the Clinical Coordinating Center.
The Hutchinson Center is also home to one of 41 WHI clinical centers nationwide. More than 3,500 women have enrolled in the study through this clinical center, which is operated jointly by the Hutchinson Center and the University of Washington. Shirley A.A. Beresford, Ph.D., serves as principal investigator of the WHI Seattle Clinical Center.
For more information about the Women's Health Initiative, please visit www.whi.org.
Fred Hutchinson Cancer Research Center
# # #
Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org.