Food-derived peptides with inhibitory capacity for HMG-CoA reductase activity: a potential nutraceutical for hypercholesterolemia

Cardiovascular diseases (CVDs) are the leading global cause of mortality and disease burden. Statins are the most prescribed lipid-lowering drugs to treat hypercholesterolemia and prevent CVDs. The biochemical mechanism of statins consists of competitive inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme (HMG-CoAR), the limiting enzyme in cholesterol biosynthesis. Due to statin intolerance in some patient groups, the search for new inhibitors is a field of great interest. This review focusses on the studies reporting the inhibitory effect of protein hydrolysates and biopeptides on the HMG-CoAR enzyme activity. The analysis of the action mechanism and physicochemical characteristics of the HMG-CoAR inhibitory peptides revealed that the molecular weight, amino acid composition, charge, and polarity are key aspects of the interaction with the HMG-CoAR enzyme. In conclusion, this review reveals the potential of using food peptides as new cholesterol-lowering agents and opens a new interesting field of research. However, clinical approaches are mandatory to confirm their therapeutic hypercholesterolemic effect. (c) 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).