Antioxidants in Cardiovascular Therapy: Panacea or False Hope?

Abstract

Oxidative stress is a key feature of the atherothrombotic process involved in the etiology of heart attacks, ischemic strokes, and peripheral arterial disease. It stands to reason that antioxidants represent a credible therapeutic option to prevent disease progression and thereby improve outcome, but despite positive findings from in vitro studies, clinical trials have failed to consistently show benefit. The aim of this review is to re-appraise the concept of antioxidants in the prevention and management of cardiovascular disease. In particular, the review will explore the reasons behind failed antioxidant strategies with vitamin supplements and will evaluate how flavonoids might improve cardiovascular function despite bioavailability that is not sufficiently high to directly influence antioxidant capacity. As well as reaching conclusions relating to those antioxidant strategies that might hold merit, the major myths, limitations, and pitfalls associated with this research field are explored.

Keywords: N-acetylcysteine; allopurinol; antioxidants; carotenoids; polyphenols; vascular disease; vitamin C; vitamin E.

Figure 1

The protective effects of antioxidants on endothelial function, LDL handling, inflammation, and thrombosis (top panel). Under conditions of oxidative stress, endothelial cell damage, loss of the protective effects of NO, and enhanced LDL peroxidation combines to drive an inflammatory state, leading to lipid accumulation in the arterial wall. CAMs, cell adhesion molecules; NOX, NAD(P)H oxidase; eNOS, endothelial NO synthase; iNOS, indicible NO synthase; NF-κB, nuclear factor kB; SOD, superoxide dismutase; ET-1, endothelin-1; CAT, catalase; GSH, glutathione; GPx, GSH peroxidase; LDL, low-density lipoprotein; ox-LDL, oxidized low density lipoprotein; ONOO⁻, peroxynitrite; ${\text{O}}_2^{\cdot -}$, superoxide; NO, nitric oxide.

Figure 2

Vitamin C (ascorbate) and its oxidation products.

Figure 3

Structure of tocopherols and tocotrienols.

Figure 4

Structure of five major carotenoids in human diet.

Figure 5

The role of vitamins B9 (folate), B6, and B12 in methionine metabolism and glutathione (GSH) synthesis.

Figure 6

Flavonoid and non-flavonoid phenolic compounds. Schematic showing phenolic compounds, along with typical examples and associated chemical structure (adapted from http://www.frenchglory.com/polyphenol-classification.html).