REVIEWS: CURRENT TOPICS The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise Jonathan M. Peake a, 4 , Katsuhiko Suzuki b,c , Jeff S. Coombes a a School of Human Movement Studies, University of Queensland, St Lucia, Brisbane, Queensland, Australia b School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan c Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan Received 22 August 2006; received in revised form 5 September 2006; accepted 4 October 2006 Abstract Interest in the relationship between inflammation and oxidative stress has increased dramatically in recent years, not only within the clinical setting but also in the fields of exercise biochemistry and immunology. Inflammation and oxidative stress share a common role in the etiology of a variety of chronic diseases. During exercise, inflammation and oxidative stress are linked via muscle metabolism and muscle damage. Because oxidative stress and inflammation have traditionally been associated with fatigue and impaired recovery from exercise, research has focused on nutritional strategies aimed at reducing these effects. In this review, we have evaluated the findings of studies involving antioxidant supplementation on alterations in markers of inflammation (e.g., cytokines, C-reactive protein and cortisol). This review focuses predominantly on the role of reactive oxygen and nitrogen species generated from muscle metabolism and muscle damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, we have analyzed the influence of factors such as the dose, timing, supplementation period and bioavailability of antioxidant nutrients. D 2007 Elsevier Inc. All rights reserved. Keywords: Cytokines; Reactive oxygen species; Muscle damage; Cortisol; C-reactive protein 1. Introduction Exercise is known to have many benefits, including preventative and therapeutic effects on a variety of chronic disorders such as diabetes mellitus; dyslipidemia; hyperten- sion; obesity; cardiovascular and pulmonary diseases; muscle, bone and joint diseases; cancer; and depression [1]. Many of these chronic disorders share a common link with chronic low-grade inflammation and overproduction of reactive oxygen and nitrogen species (RONS) [2]. Increas- ing evidence suggests that the health benefits of exercise are partly linked to reduced levels of inflammation and oxidative stress [3,4]. It is well accepted that the health benefits of exercise are enhanced by positive dietary modification. The relationship between inflammation and oxidative stress has generated interest in the benefits of antioxidant supplements in health and disease, as well as athletic performance and adaptation to training. Over the years, exercise scientists have examined the potential effect of antioxidant nutrients to counter the influence of RONS on muscle damage, muscle fatigue, lipid peroxidation and damage to cellular proteins and DNA during exercise. However, attention has more recently shifted toward the specific interaction between antioxidant nutrients, redox-sensitive signaling pathways and inflammatory responses to exercise. Evidence suggests that antioxidant supplementation may in fact attenuate some of the exercise-induced cellular signals that stimulate adaptations in vascular tissue and skeletal muscle also exists [5,6]. The number of studies that have investigated this issue has risen in recent years, and this has stimulated interesting debate [7–11]. The aim of this review article is to collate and review the findings of studies that have examined the effects of antioxidant supplements on inflammatory responses to exercise. In the first part of this review, we have briefly discussed the mechanisms that contribute to cytokine changes during exercise. This is followed by a short discussion of the mechanisms of production of RONS 0955-2863/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2006.10.005 4 Corresponding author. Tel.: + 61 7 3365 3401; fax: + 61 7 3365 6877. E-mail address: jpeake@hms.uq.edu.au (J.M. Peake). Journal of Nutritional Biochemistry 18 (2007) 357 – 371