In the Women's Health Initiative Dietary Modification Trial, nearly 50,000 postmenopausal women were randomly assigned to a low-fat dietary pattern or to a usual diet comparison group. The 8.3-year intervention period ended in 2005, but all participants were followed for mortality through 2013. Incidence rates for cardiovascular disease (CVD) did not differ between the intervention and comparison groups.
Several studies have compared low carbohydrate and low fat diets in obesity. In one representative study, a one-year, multicenter, controlled trial randomized 63 men and women with obesity to either a low-carbohydrate diet or a low-calorie, high-carbohydrate, low-fat (conventional) diet. Subjects on the low carbohydrate diet lost more weight than subjects on the low fat diet at 3 and 6 months, but the difference at 12 months was not significant. No differences were found between the groups in total cholesterol or low density lipoprotein (LDL) cholesterol concentrations.
The increase in HDL cholesterol concentrations and the decrease in triglyceride concentrations were greater on the low carbohydrate diet compared to the conventional diet during most of the study. In a subsequent paper from the same researchers randomizing 307 persons for two years, weight loss was similar between diet strategies, but the major lipid difference at the two-year time point was lower triglycerides in the low carbohydrate group. These lipid changes have been consistent across many studies. In such research, adherence tends to be poor with high attrition, hence a paucity of long-term (i.e., 5-year) data.A meta-analysis of 23 trials from multiple countries containing more than 2500 randomized participants concluded that both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with subjects on low fat diets, persons on low carbohydrate diets had a slight benefit with regard to total cholesterol and LDL, but achieved a greater increase in HDL and a greater decrease in triglycerides. Reductions in body weight, waist circumference, and other metabolic risk factors were not different between the two diets.