A Review of Low-Density Lipoprotein-Lowering Diets in the Age of Anti-Sense Technology

• Published in: Nutrients Vol. 15; no. 5; p. 1249
• Main Authors: Nestel, Paul J, Mori, Trevor A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Anticholesteremic Agents - therapeutic use; Antisense therapy; Arteriosclerosis; Atherosclerosis; Carbohydrates; Cardiovascular disease; Cardiovascular diseases; Causes of; Cholesterol; Cholesterol, LDL; cholesterol-lowering technologies; Clinical trials; Control; Diet; Diet therapy; dietary approaches; Energy; Fatty acids; Health aspects; Health risks; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia; Hypercholesterolemia - drug therapy; Industrial development; Kexin; Lipid metabolism; Lipids; Lipoproteins; Low density lipoprotein; Medical personnel; Methods; Monoclonal antibodies; Mortality; Nutrient deficiency; Nutrition research; Nuts; Oils & fats; Pharmacology; Phytosterols; Plasma; Proprotein Convertase 9; Proprotein convertases; Review; RNA-mediated interference; Statins; Subtilisin; Triglycerides; Vegetable oils; Australia; China; cholesterol-lowering technologies; dietary approaches; hypercholesterolemia
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15051249

This narrative review discusses an important issue, the primary role of diet in reducing low-density lipoprotein cholesterol (LDLc) concentrations in polygenic hypercholesterolemia. Two effective drugs, statins, and ezetimibe, that lower LDLc > 20% are relatively inexpensive and potential competitors to strict dieting. Biochemical and genomic studies have shown that proprotein convertase subtilisin kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) and lipid metabolism. Clinical trials have demonstrated that inhibitory monoclonal antibodies of PCSK9 dose-dependently lower LDLc up to 60%, with evidence of both regression and stabilization of coronary atherosclerosis and a reduction in cardiovascular risk. Recent approaches using RNA interference to achieve PCSK9 inhibition are currently undergoing clinical evaluation. The latter presents an attractive option of twice-yearly injections. They are, however, currently expensive and unsuitable for moderate hypercholesterolemia, which is largely due to inappropriate patterns of eating. The best dietary approach, the substitution of saturated fatty acids by polyunsaturated fatty acids at 5% energy, yields > 10% lowering of LDLc. Foods such as nuts and brans, especially within a prudent, plant-based diet low in saturates complemented by supplements such as phytosterols, have the potential to reduce LDLc further. A combination of such foods has been shown to lower LDLc by 20%. A nutritional approach requires backing from industry to develop and market LDLc-lowering products before pharmacology replaces the diet option. Energetic support from health professionals is vital.