WHI Low-Fat Dietary Trial: What a Billion-Dollar Trial Showed that Epidemiology Already Knew

[Epidemiologic Inquiry 2006, 1: 15]

As they say in baseball and criminal felonies- "3 strikes and you're out" - however, is this adage necessary true? In a recent blockbuster issue of JAMA, investigators from the decade-long Women's Health Initiative low-fat dietary trial simultaneously reported the results for breast cancer, colorectal cancer, and cardiovascular disease... in essense, results indicated no overall benefit of a low-fat dietary pattern.

This opens lots of questions: Was the trial worth the multi-million dollar investment? Was there any gain from the trial? What were major limitations in this trial? Should this trial have been conducted in the first place?

Over a decade ago, when scientists first began proposing and planning this low-fat trial, FAT was the hottest craze in medical science. Total fat, not giving regard to types of fat, was deemed the key culprit to chronic diseases. However, around the same time, many large prospective epidemiologic studies had consistently found that total fat was NOT associated with breast cancer, total fat was NOT associated with colorectal cancer, and total fat was NOT associated with cardiovascular disease.

Nevertheless, several vocal advocates pushed such a low-fat trial through the NIH by lobbying Congress, despite mounting scientific evidence that it was not total fat per se, but rather different types of fats that differentially influenced the risk of such diseases. Notably, trans-fat was already known in the early 1990s that it increased the risk of CVD, while other unsaturated fats were more beneficial for CVD. Differences in types of fat was also being recognized for cancer risks. Thus, 10 years late, the trial ultimately found what epidemiologists already knew all along about total fat.

As for the WHI low-fat trial itself- it had many limitations. Its study protocol specified that women reduce their fat intake to <20% size="2">Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
Prentice et al.
JAMA. 2006; 295:629-642.

Low-Fat Dietary Pattern and Risk of Colorectal Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
Beresford et al.
JAMA. 2006; 295:643-654.

Low-Fat Dietary Pattern and Risk of Cardiovascular Disease: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
Howard et al.
JAMA. 2006; 295:655-666.