1. Tiukinhoy, Susan MD, MS
  2. Rochester, Carolyn L. MD

Article Content

Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil-Smoller S, Kuller LH, LaCroiz AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw J, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf AR, Bassford T, Beresford SAA, Black HR, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss G, Hendrix SL, Hubbell A, Johnson KC, Kotchen JM


JAMA. 2006;295(6):655-666.



Epidemiologic studies have demonstrated that diets low in saturated fat and cholesterol are associated with lower rates of cardiovascular disease (CVD). Replacing saturated fat with polyunsaturated fat reduced cardiovascular (CV) events in some early trials. A Mediterranean-type dietary pattern or a very low-fat eating pattern also prevented recurrent CV events. Whether a single 'healthy' diet could result in decreased risks of both cancer and CVD is not known.



The primary aim of the Women's Health Initiative (WHI) Dietary Modification Trial was to test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruit, and grains, would reduce the incidence of breast and colorectal cancer. This study reports on findings designed to address the secondary aim of the project, which was to test whether the same dietary intervention would also reduce the risk of CVD.



This was a randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, consuming a diet at baseline with fat intake of >=32% of total calories. Subjects were randomized to a dietary intervention group or a usual-diet comparison group. Dietary intervention was designed to promote dietary changes with the goal of reducing total fat intake to 20% of caloric intake by increasing intake of vegetables, fruits, and grains. This involved an intensive behavioral modification program with 18 group sessions in the first year, and quarterly maintenance sessions thereafter. Group activities were supplemented by individual interviews and targeted-message campaigns. Women in the comparison group received diet-related education materials, but had no contact with the nutrition interventionists. Main outcome measures included fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and the composite of CHD and stroke.



The mean follow-up for this study was 8.1 years. Compared with the comparison group, the dietary intervention group reported significant changes in all dietary components resulting in an 8.2% lower mean total fat intake (P < .001), and a 2.9% lower mean saturated fat intake (P < .001). They also had reduced intakes of trans, mono-unsaturated, and polyunsaturated fat and cholesterol, and increased intakes of fiber, vegetables and fruits, total and whole grains, and soy. Women in the intervention group showed small but significant decreases in body weight, waist circumference, diastolic blood pressure, and low-density cholesterol (LDL-C) levels compared to the comparison group. There were no significant effects on levels of triglycerides or high-density cholesterol, glucose, or insulin and insulin resistance. The diet had no significant effects on incidence of CHD (HR = 0.97; 95% CI 0.90-1.06), stroke (HR = 1.02; 95% CI 0.90-1.15), or the composite of CHD and stroke (HR = 0.98; 95% CI0 .92-1.05). Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat, or higher intakes of vegetables and fruits.



The WHI Dietary Modification Trial is the largest long-term randomized trial of a dietary intervention conducted. This study showed that a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or the composite of CHD and stroke in postmenopausal women and achieved only modest effects on CVD risk factors. This study focused on women aged between 50 and 79 years, and the possibility that the effect would have been different in men or if the diet had been initiated at younger ages is not known. To achieve a significant public health impact on CVD events, a greater magnitude of change in multiple macronutrients and micronutrients and other behaviors that influence CVD risk factors may be necessary.



Two important factors need to be considered regarding this study. One is that the primary aim of the dietary intervention was cancer prevention. Hence, the study was not designed to specifically reduce intake of fats known to reduce CVD risk. There was also no effort to emphasize fish intake. A major assumption of the trial design was that aiming to reducetotal fat intake to 20% of energy intake would alsoresult in a reduction in saturated fat intake. There were only small decreases in saturated fat intake in the intervention cohort, which was reflected in the minimal change in LDL-C levels seen, which in turn predicts a small reduction in CVD risk. Secondly, the dietary intervention accomplished only approximately 70% of the design assumptions regarding the difference in percentage energy from fat achieved in the intervention group. This, coupled with the fact that the incidence rate for the major outcomes in the comparison group was approximately two thirds of the rate assumed in the trial design, resulted in a projected power of only 40% to detect differences between groups. This study does not negate the common-sense notion that a low-fat diet is beneficial in reducing CVD risk. It does suggest, however, that studies are needed to address interventions that effect reductions in specific fats known to affect CVD risk.