Randomized trials of replacing saturated fatty acids with n-6 polyunsaturated fatty acids in coronary heart disease prevention: Not the gold standard?

Several trials in the 1950s through 1970s tested the hypothesis that replacing saturated fat in the diet predominantly with n-6 polyunsaturated fat (PUFA) would reduce the incidence of coronary heart disease (CHD), mainly through modifying blood lipid profile. Most of these trials did observe a reduction in serum total cholesterol in the intervention group, but many trials failed to find a significant reduction in the incidence of CHD. However, some meta-analyses have found a reduced incidence of CHD by pooling the results from the trials. Recently, new recovered and reanalyzed data has emerged from two of the old trials. The new findings seemed to counteract the classical diet-heart hypothesis, when they found no cardiovascular benefit and even suggested harm, despite reduction in the serum total cholesterol concentration after replacing saturated fat especially with n-6 PUFA. This has raised criticism regarding the validity of the dietary recommendations that suggest partially replacing saturated fats with n-6 PUFA. This paper introduces the classical diet-heart trials and their main results and how the new findings relate to the overall study data of the cardiovascular effects of the n-6 PUFA. For multiple reasons considered here, it is difficult to draw firm conclusions of the cardiovascular effects of the n-6 PUFA based only on the findings in the old diet-heart trials. A more comprehensive picture emerges when also other lines of evidence is considered. The overall study data, including findings also from prospective cohort studies and from dietary trials with intermediate outcomes, still suggests that replacing saturated fat with n-6 PUFA would rather be beneficial than harmful for the prevention of CHD.