Long‐Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E‐Knockout Mice

Scope HDL particles are protective against atherosclerosis, but may become dysfunctional during inflammation and chronic disease progression. Anthocyanin‐rich foods, such as the black elderberry, may improve HDL function and prevent disease development via antioxidant and/or anti‐inflammatory effects. This study investigates the long‐term consumption of black elderberry extract (BEE) on HDL function and atherosclerosis in apolipoprotein (apo) E −/− mice. Methods and Results ApoE −/− mice ( n = 12/group) are fed a low‐fat diet, supplemented with 0, 0.25%, or 1% (by weight) BEE (≈37.5–150 mg anthocyanins per kg body weight) for 24 weeks. Feeding 1% BEE increases total serum cholesterol (+31%) and non‐HDL cholesterol (+32%) compared with the control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increase with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increase HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose‐dependently lowers serum liver enzymes and hepatic inflammatory gene expression. Although there is no change in neutral lipid accumulation in atherosclerotic lesions, BEE promotes connective tissue deposition in the aortic root. Conclusions Chronic BEE supplementation in apoE −/− mice dose‐dependently improves HDL function. Despite BEE promoting hyperlipidemia, which likely offsets HDL effects, BEE increases connective tissue content, suggesting improved atherosclerotic plaque stability.