IntroductionCardiovascular disease (CVD) is the leading cause of death worldwide. The total number of cardiovascular disease cases nearly doubled from 1990 to 2019 from 271 million to 523 million.1 One of the main treatments for hyperlipidemia and CVD is a reduction in low density lipoprotein cholesterol (LDL-C). Multiple drugs are available on the market that reduce LDL-C including statins, proprotein convertase kexin/subtilisin type 9 (PCSK9) inhibitors, and ezetimibe. Statins are the most widely prescribed drug in this class. Moderate statin therapy has been shown to reduce LDL-C levels by 30-45%, while high-intensity statin therapy can provide reductions of over 50%.2However, some patients, such as those with familial hypercholesterolemia (FH), cannot reach target LDL-C goals with statin therapy alone. Both the American Heart Association and the European Atherosclerosis Society recommend ezetimibe and PCSK9 inhibitors as secondary treatments for at-risk patients with insufficient LDL-C reductions.3An alternate approach to cholesterol reduction involves using natural products, which are often less costly than their synthetic counterparts and tend to have fewer side effects. The natural compound berberine (Figure 1) is of particular interest for several reasons. First, it lowers cholesterol via multiple pathways.4–9Furthermore, it attenuates inflammation associated with CVD,10,11 Alzheimer’s disease (AD),12–14 and diabetes15,16 by reducing pro-inflammatory cytokines. It is also effective in treating cancer cells17,18. This suggests that it could improve health outcomes for multiple diseases simultaneously.