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

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.

Automated summary

This narrative review focuses on the role of diet in reducing LDLc concentrations in polygenic hypercholesterolemia. Statins and ezetimibe are effective drugs that can lower LDLc by more than 20%, providing potential alternatives to strict dieting. PCSK9 plays a significant role in LDL and lipid metabolism, and inhibitory monoclonal antibodies have shown promising results in lowering LDLc. A nutritional approach, such as substituting saturated fats with polyunsaturated fats, along with incorporating specific foods and supplements, has the potential to further reduce LDLc. Industry support and proper guidance from health professionals are necessary for the development and promotion of LDLc-lowering products.