Recent Molecular Mechanisms and Beneficial Effects of Phytochemicals and Plant-Based Whole Foods in Reducing LDL-C and Preventing Cardiovascular Disease

Abstract

Abnormal lipid metabolism leads to the development of hyperlipidemia, a common cause of multiple chronic disorders, including cardiovascular disease (CVD), obesity, diabetes, and cerebrovascular disease. Low-density lipoprotein cholesterol (LDL-C) currently remains the primary target for treatment of hyperlipidemia. Despite the advancement of treatment and prevention of hyperlipidemia, medications used to manage hyperlipidemia are limited to allopathic drugs, which present certain limitations and adverse effects. Increasing evidence indicates that utilization of phytochemicals and plant-based whole foods is an alternative and promising strategy to prevent hyperlipidemia and CVD. The current review focuses on phytochemicals and their pharmacological mode of actions for the regulation of LDL-C and prevention of CVD. The important molecular mechanisms illustrated in detail in this review include elevation of reverse cholesterol transport, inhibition of intestinal cholesterol absorption, acceleration of cholesterol excretion in the liver, and reduction of cholesterol synthesis. Moreover, the beneficial effects of plant-based whole foods, such as fresh fruits, vegetables, dried nuts, flax seeds, whole grains, peas, beans, vegan diets, and dietary fibers in LDL-C reduction and cardiovascular health are summarized. This review concludes that phytochemicals and plant-based whole foods can reduce LDL-C levels and lower the risk for CVD.

Keywords: CVD; LDL; cholesterol; dietary fiber; hyperlipidemia; lipid oxidation; plant-based foods.

Figure 1

Connection between LDL and CVD.

Figure 2

Acceleration of RCT by various phytochemicals.

Figure 3

Phytochemicals block the absorption of intestinal cholesterol.

Figure 4

Phytochemicals inhibit the synthesis of cholesterol.

Figure 5

Mechanisms of dietary fiber in the gut. Dietary fibers are carbohydrate polysaccharides; not hydrolyzed by digestive enzymes in gastrointestinal tract and are associated with a low risk for CVD. (A) Dietary fibers elevate the fecal excretion of bile acid, decrease its re-uptake in the small intestine, and inhibit bile acid permeation. A reduced enterohepatic pool of bile acid stimulates the CYP7A (the rate-limiting enzyme involved in the production of bile acid), which, in turn, enhances liver uptake of LDL-C from blood through the upregulation of LDL-R and HMGCR. (B,C) Dietary fibers exhibit fewer calories and their consumption results in a prolonged digestion time with delayed gastric emptying. Additionally, it leads to an increase in bulk-forming and satiety, as well as viscosity-induced reduced absorption of cholesterol, which eventually lower the concentration of LDL-C. (D) Reduced cholesterol synthesis from SCFAs, produced by dietary fibers fermentation in the intestine, contributes to decrease the concentration of LDL-C. Certain SCFAs (propionate) enhances the release of PYY and GLP-1, both of which contribute to reduce LDL-C concentration. Additionally, dietary fibers intake leads to reduced fat uptake, altering the production of adipokines (TNF-α, resistin, and leptin), which play key roles in lipid metabolism and improving cholesterol concentration. The viscosity of dietary fibers reduces the intestinal absorption of glucose, leading to decreased secretion of insulin. Insulin is responsible for stimulating HMGCR; thus, lower insulin could decrease the concentration of LDL-C.