Roger Clemens

Recent wildly contradictory headlines from the clinical literature question what the public is to believe, how clinical investigators and research funding agencies adjust and conceive hypotheses and study designs, and what health professionals are to recommend to consumers and patients.

The mixed messages include “fat is risky” and “fat is good.” Clearly, the real questions are how do we read the simplistic and sensational headlines and how do we interpret the studies? How do we maintain some measure of balance in the evidence based on what data may be valuable and relevant?

Let’s examine some of the evidence relative to women’s health and diet.

The Nurses’ Health Study, launched by the National Institutes of Health in 1976, intended to investigate the long-term consequences of oral contraceptives, was modified in 1980 and 1989 because of the compelling evidence linking diet, nutrition, and lifestyle to the development of chronic disease. Subsequent followup among 125,000 premenopausal women initially free of cardiovascular disease, diabetes, and cancer suggested (1) that an inverse relation existed between polyunsaturated fat intake and coronary heart disease risk, particularly among younger or overweight women, and (2) that intakes of total fat and fiber were not significantly related to risk of breast cancer, yet vegetable fat, vitamin E, and fiber intakes during adolescence were inversely associated with risk of proliferative benign breast disease.

The Women’s Health Initiative, consisting of major clinical trials and large observational studies funded by NIH, examined nearly 50,000 postmenopausal women relative to dietary and behavioral intervention and the risk of cancer and cardiovascular disease. Recent headlines based on clinical results from this initiative (see the February 8, 2006, issue of JAMA) indicated that after an average eight years of followup on these women, a low-fat, high-fiber dietary intervention did not yield a significant reduction in breast cancer, colon cancer, or heart disease. These conclusions require several points of clarification, critical assessment of the data, and closer examination of the disease process.

• Dietary interventions called for a fat reduction to less than 20% of total calories. In fact, the low-fat group reduced total fat intake from approximately 38% to nearly 29% of total energy.

• Within the low-fat group, there was a 9% lower risk for invasive breast cancer among women 50–79 years old during the followup period.

• Decreased energy from fat and increased vegetable, fruit, and grain intake did not significantly reduce the risk of invasive colorectal cancer in post-menopausal women. However, in secondary analysis among those using aspirin and hormone replacement therapy, there was a 9% reduction in the self-report of colorectal polyps or adenomas during the study period.

• Among the intervention group, there was an observed trend toward the reduction of cardiovascular disease risk among those consuming the lower levels of dietary fat and higher amounts of fruits and vegetables at year 1.

• Higher-carbohydrate, lower-fat dietary practices appeared to increase body weight or augment risk factors, such as elevated triglycerides and glucose associated with insulin resistance and diabetes.

• Dietary assessment did not differentiate among the various kinds of fat intake. However, there were reductions in saturated, trans fatty acids, polyunsaturated fat, and monounsaturated fat within the intervention group.

• Disease development is typically a long-term process, especially when considering some forms of cancer and cardiovascular disease, not to mention metabolic bone disease and diabetes. The dietary intervention of eight years is too short to adequately assess the potential clinical benefit of interventions on these disease processes.

Despite the methodologic limitations of epidemiologic research, these two large studies among women suggest that risk reduction of breast cancer and cardiovascular disease through dietary intervention and lifestyle modifications is meaningful and should begin during the earlier decades of life. Those modifications that help in maintaining a desirable body weight, remaining physically active, and following current dietary guidelines will be studied further and hopefully will be clarified and communicated to the public.

Reading and interpreting public health investigation is at least as challenging as conceiving and executing it. We must all focus critical eyes on data and on the complex relationships between variables, many of which are not intuitively obvious and which ultimately then justify the effort and funding of this kind of research.

by Roger Clemens, Dr.P.H.,
Contributing Editor Director,
Analytical Research, Professor,
Molecular Pharmacology & Toxicology, USC School of Pharmacy, Los Angeles, Calif.
[email protected]

by Peter Pressman, M.D.,
Contributing Editor Attending Staff,
Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif.
[email protected]