Background Walnuts have beneficial effects on cardiovascular risk factors, but it is unclear whether these effects are attributable to the fatty acid ( FA ) content, including α-linolenic acid ( ALA ), and/or bioactives. Methods and Results A randomized, controlled, 3-period, crossover, feeding trial was conducted in individuals at risk for cardiovascular disease (n=45). Following a 2-week standard Western diet run-in (12% saturated FAs [ SFA ], 7% polyunsaturated FAs, 12% monounsaturated FAs), participants consumed 3 isocaloric weight-maintenance diets for 6 weeks each: a walnut diet ( WD ; 7% SFA , 16% polyunsaturated FAs, 3% ALA , 9% monounsaturated FAs); a walnut FA -matched diet; and an oleic acid-replaced- ALA diet (7% SFA , 14% polyunsaturated FAs, 0.5% ALA , 12% monounsaturated FAs), which substituted the amount of ALA from walnuts in the WD with oleic acid. This design enabled evaluation of the effects of whole walnuts versus constituent components. The primary end point, central systolic blood pressure, was unchanged, and there were no significant changes in arterial stiffness. There was a treatment effect ( P=0.04) for central diastolic blood pressure; there was a greater change following the WD versus the oleic acid-replaced-ALA diet (-1.78±1.0 versus 0.15±0.7 mm Hg, P=0.04). There were no differences between the WD and the walnut fatty acid-matched diet (-0.22±0.8 mm Hg, P=0.20) or the walnut FA-matched and oleic acid-replaced-ALA diets ( P=0.74). The WD significantly lowered brachial and central mean arterial pressure. All diets lowered total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, and non- HDL cholesterol. Conclusions Cardiovascular benefits occurred with all moderate-fat, high-unsaturated-fat diets. As part of a low- SFA diet, the greater improvement in central diastolic blood pressure following the WD versus the oleic acid-replaced-ALA diet indicates benefits of walnuts as a whole-food replacement for SFA . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT02210767.
Keywords: arterial stiffness; bioactives; nutrition; polyunsaturated fatty acids; pulse‐wave velocity; walnuts; α‐linolenic acid.