BackgroundNut consumption lowers cardiovascular disease (CVD) risk. Studies are lacking about the effects of pistachios, a nutrient-dense nut, on CVD risk factors, dose-response relations, and lipid-lowering mechanisms. ObjectiveWe evaluated the effects of 2 doses of pistachios, added to a lower-fat diet, on lipids and lipoproteins, apolipoprotein (apo)-defined lipoprotein subclasses, and plasma fatty acids. To investigate the mechanisms of action, we measured cholesteryl ester transfer protein and indexes of plasma stearoyl-CoA desaturase activity (SCD). DesignIn a randomized crossover controlled-feeding study, 28 individuals with LDL cholesterol ≥ 2.86 mmol/L consumed 3 isoenergetic diets for 4 wk each. Baseline measures were assessed after 2 wk of a typical Western diet. The experimental diets included a lower-fat control diet with no pistachios [25% total fat; 8% saturated fatty acids (SFAs), 9% monounsaturated fatty acids (MUFAs), and 5% polyunsaturated fatty acids (PUFAs)], 1 serving/d of a pistachio diet (1 PD; 10% of energy from pistachios; 30% total fat; 8% SFAs, 12% MUFAs, and 6% PUFAs), and 2 servings/d of a pistachio diet (2 PD; 20% of energy from pistachios; 34% total fat; 8% SFAs, 15% MUFAs, and 8% PUFAs). ResultsThe 2 PD decreased (P < 0.05 compared with the control diet) total cholesterol (−8%), LDL cholesterol (−11.6%), non-HDL cholesterol (−11%), apo B (−4%), apo B/apo A-I (−4%), and plasma SCD activity (−1%). The 1 PD and 2 PD, respectively, elicited a dose-dependent lowering (P < 0.05) of total cholesterol/HDL cholesterol (−1% and −8%), LDL cholesterol/HDL cholesterol (−3% and −11%), and non-HDL cholesterol/HDL cholesterol (−2% and −10%). ConclusionsInclusion of pistachios in a healthy diet beneficially affects CVD risk factors in a dose-dependent manner, which may reflect effects on SCD.