Effect of n-3 Fatty Acids and Antioxidants on Oxidative Stress after Exercise STEVEN R. MCANULTY 1 , DAVID C. NIEMAN 1 , MASHA FOX-RABINOVICH 2 , VALERIE DURAN 2 , LISA S. MCANULTY 2 , DRU A. HENSON 3 , FUXIA JIN 4 , and MICHAEL J. LANDRAM 1 1 Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC; 2 Department of Family and Consumer Science, Appalachian State University, Boone, NC; 3 Department of Biology, Appalachian State University, Boone, NC; and 4 Chemistry, Appalachian State University, Boone, NC ABSTRACT MCANULTY, S. R., D. C. NIEMAN, M. FOX-RABINOVICH, V. DURAN, L. S. MCANULTY, D. A. HENSON, F. JIN, and M. J. LANDRAM. Effect of n-3 Fatty Acids and Antioxidants on Oxidative Stress after Exercise. Med. Sci. Sports Exerc., Vol. 42, No. 9, pp. 1704–1711, 2010. Purpose: n-3 fatty acids are known to exert multiple beneficial effects including anti-inflammatory actions that may diminish oxidative stress. Supplementation with antioxidant vitamins has been proposed to counteract oxidative stress and improve antioxidant status. Therefore, this project investigated the effects of daily supplementation in 48 trained cyclists over 6 wk and during 3 d of continuous exercise on F 2 -isoprostanes (oxidative stress), plasma n-3 fatty acids, and antioxidant status (oxygen radical absorption capacity and ferric-reducing antioxidant potential). Methods: Cyclists were randomized into n-3 fatty acids (N3) (n = 11) (2000 mg of eicosapentaenoic acid and 400 mg of docosahexaenoic acid), a vitamin–mineral (VM) complex (n = 12) emphasizing vitamins C (2000 mg), E (800 IU), A (3000 IU), and selenium (200 Kg), a VM and n-3 fatty acid combination (VN3) (n = 13), or placebo (P) (n = 12). Blood was collected at baseline and preexercise and postexercise. A 4 Â 3 repeated-measures ANOVA was performed to test main effects. Results: After exercise, F 2 -isoprostanes were higher in N3 (treatment effect P = 0.014). Eicosapentaenoic acid and docosahexaenoic acid plasma values were higher after supplementation (interaction effect P = 0.001 and 0.006, respectively) in both n-3 supplemented groups. Oxygen radical absorption capacity declined similarly among all groups after exercise. Ferric-reducing antioxidant potential exhibited significant interaction (P = 0.045) and significantly increased after exercise in VN3 and VM (P G 0.01). Conclusions: This study indicates that supplementation with n-3 fatty acids alone significantly increases F 2 -isoprostanes after exhaustive exercise. Lastly, antioxidant supplementation augments plasma antioxidant status and modestly attenuates but does not prevent the significant n-3 fatty acid associated increase in F 2 -isoprostanes postexercise. Key Words: EICOSAPENTAENOIC ACID, DOCOSAHEXAENOIC ACID, F 2 -ISOPROSTANES, CYCLING O mega-3 fatty acids (n-3fa) comprise a family of unsaturated fatty acids that consist of >-linolenic acid, eicosapentaenoic acid (EPA), and docosa- hexaenoic acid (DHA), which are essential nutrients that must be obtained from food because of the inability of humans to synthesize these fatty acids de novo (28). Human beings evolved consuming a diet that contained about equal amounts of omega-6 (n-6fa) and n-3fa fatty acids. Current western diets provide ratios of n-6fa to n-3fa ranging from approximately 10:1 to 20:1 instead of the traditional range of 1:1 to 2:1, respectively. It is known that a high intake of n-6fa increases prothrombotic and proaggregatory activities characterized by increases in blood viscosity and vasospasm and vasoconstriction (27). Given that n-3fa exhibit anti- inflammatory, antithrombotic, antiarrhythmic, hypolipide- mic, and vasodilatory properties, an increased consumption of n-3fa would likely be beneficial (27). Although n-3fa have potential benefits against certain diseases such as cardiovascular disease, Alzheimer’s dis- ease, Parkinson’s disease, diabetes mellitus, essential hyper- tension, and atherosclerosis, questions remain about the effect on subsequent oxidative stress if supplemented alone or in conjunction with other antioxidants (4,8,15,26). Specifically, increased consumption of n-3fa may lead to increased lipid peroxidation (18). Thus far, the data obtained in vivo are not conclusive for (18) or against (1) increased lipid peroxidation with n-3 fatty acid supplemen- tation. Furthermore, a study that has examined n-3fa sup- plementation and oxidative damage with exercise has not been conducted to our knowledge. Therefore, it is not known whether heavily exercising athletes should supple- ment with n-3fa. It is well established that a causal link exits between oxidative stress and various disease states such as cancer and heart disease (2,7). Routine exercise is generally regarded as Address for correspondence: Steven R. McAnulty, Ph.D., Dept HLES, PO Box 32071, Appalachian State University, Boone, NC 28608; E-mail: mcanltysr@appstate.edu. Submitted for publication September 2009. Accepted for publication February 2010. 0195-9131/10/4209-1704/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE Ò Copyright Ó 2010 by the American College of Sports Medicine DOI: 10.1249/MSS.0b013e3181d85bd1 1704 BASIC SCIENCES Copyright © 2010 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.