OTC Antioxidant Products for the Treatment of Cardiovascular and other Disorders: Popular Myth or Fact?

Abstract

Cardiovascular disease (CVD) is the number one cause of mortality worldwide as reported by World Health Organization (WHO), Centers for Disease Control (CDC) and American Heart Association (AHA). The role of micronutrients has been studied extensively as CVD risk minimizing intervention. Among these, dietary supplements antioxidants available over the counter are highly commercialized but scientific evidences and clinical trials supporting their use is not conclusive yet [1]. The beneficial effects of these antioxidants are focused mainly against pathogenesis of atherosclerosis, as the primary contributor to coronary artery disease and resulting cardiovascular complications. Atherosclerosis is chronic inflammatory process of deposition of fatty cholesterol filled plaque in arterial wall which narrows the diameter and obstructs blood flow down the length of coronary artery and throughout its branches. Hyperlipidemia (high HDL: LDL ratio), high blood pressure, toxins from tobacco are assumed to be the major risk factor of atherosclerosis. If plasma LDL exceeds the regulatory capacity of endothelial cells, LDL crosses the endothelial barrier and trapped in sub-endothelial space where they are susceptible for oxidation by reactive oxygen species (ROS) - superoxide anion (·O2−), hydroxyl radical (OH·), hydrogen peroxide (H2O2), reactive nitrogen species (RNS), nitric oxide (NO) and peroxynitrite (ONOO·) released by endothelial cells and macrophages [2]. These modified LDL stimulates endothelial cells to express various cell adhesion molecules (VCAM-I, P-selectin etc.) and chemotactic factors (monocyte chemotactic factor-1, MCP-1) for the recruitment of monocytes. Monocyte attachment is initiated by P-selectin on endothelial cell upon binding with P-selectin glycoprotein ligand-1 (PSGL-1) on the monocytes leading to rolling and prolonging the contact of monocyte on the arterial wall and initiate diapedesis across endothelial layers. Monocytes differentiate into macrophages under the influence of monocyte colony stimulating factor (M-CSF). Oxidized LDL is then engulfed in an unregulated fashion by macrophage scavenger receptor resulting in intracellular accumulation of cholesterol and forms foam cell formation [3,4]. Macrophages are also involved in activation of T cells to amplify the inflammatory response by secreting TNF-α and INF-γ. Finally, smooth muscle cells proliferate and migrate from tunica media and shield the fatty plaque and synthesize collagen to form a fibrous cap [5–7].