Forum: Oxidative Stress Status TOTAL ANTIOXIDANT CAPACITY AS A TOOL TO ASSESS REDOX STATUS: CRITICAL VIEW AND EXPERIMENTAL DATA ANDREA GHISELLI,MAURO SERAFINI,FAUSTA NATELLA, and CRISTINA SCACCINI National Institute for Food and Nutrition Research (Istituto Nazionale per la Ricerca su Alimenti e Nutrizione), 546 Via Ardeatina, 00178 Rome, Italy (Received 15 November 1999; Revised 27 June 2000; Accepted 12 July 2000) Abstract—The measure of antioxidant capacity (AC) considers the cumulative action of all the antioxidants present in plasma and body fluids, thus providing an integrated parameter rather than the simple sum of measurable antioxidants. The capacity of known and unknown antioxidants and their synergistic interaction is therefore assessed, thus giving an insight into the delicate balance in vivo between oxidants and antioxidants. Measuring plasma AC may help in the evaluation of physiological, environmental, and nutritional factors of the redox status in humans. Determining plasma AC may help to identify conditions affecting oxidative status in vivo (e.g., exposure to reactive oxygen species and antioxidant supplementation). Moreover, changes in the plasma AC after supplementation with galenic antioxidants or with antioxidant-rich foods may provide information on the absorption and bioavailability of nutritional compounds. Consequently, this review discusses the rationale, interpretation, confounding factors, measurement limits, and human applications of the measure of plasma AC. © 2000 Elsevier Science Inc. Keywords—Free radical, Antioxidant capacity, Oxidative stress, Plasma, Uric acid, Plant phenols INTRODUCTION The increasing evidence that reactive oxygen species (ROS) and oxidative damage is involved in several in- flammatory and degenerative diseases [1] has recently stimulated much interest and concern. Oxidative damage can originate from an increase in free radical production either by exogenous radicals such as radiation, pollution, and cigarette smoking, or by endogenous sources, such as inflammation, the respiratory burst, and xenobiotic killing [1]. Mammals have evolved complex antioxidant strate- gies to utilize oxygen and to minimize the noxious ef- fects of its partially reduced species [2]. Antioxidants within cells, cell membranes, and extracellular fluids can be upregulated and mobilized to neutralize excessive and inappropriate ROS formation. Within the strategy to maintain redox balance against oxidant conditions (e.g., chronic inflammation, cigarette smoking, and diets poor in antioxidants and/or rich in pro-oxidants) [3,4], blood has a central role because it transports and redistributes antioxidants to every part of the body. For example, plasma can scavenge long-lived ROS, such as the super- Andrea Ghiselli, M.D., specialized in Internal Medicine, has been a researcher at the Istituto Nazionale di Ricerca su Alimenti e Nutrizione (INRAN) since 1989. He works in the field of antioxidant modulation of platelet function and cardiovascular diseases and currently conducts studies in humans on oxidative stress and dietary antioxidants. In 1996, he actively contributed to the establishment of the Free Radical Re- search Group (http://inn.ingrm.it/frrg.htm). Mauro Serafini, Ph.D. in Experimental Physiopathology, is a re- searcher at the INRAN. Previously, he was a post-doctoral fellow at the faculty of Pharmacy of the University of Coimbra, and a visiting scientist at the Nutritional Immunology Lab of the Human Nutrition Research Center on Aging (HNRC) at Tufts University. His interests are in the dietary modulation of oxidative stress in humans and on the redox modulation of cell-mediated immune function. Fausta Natella is a post-doctoral fellow in the Free Radical Research Group at INRAN. She received her Degree in Biological Sciences at the University of Rome (1996). She is currently involved in research on the oxidative modification of LDL and the antioxidant activity of phenolic compounds in different model systems. Cristina Scaccini has been a senior scientist at the INRAN since 1993. Prior to this she held a research scientist position at the Center for Human Nutrition—Southwestern Medical School, University of Texas at Dallas (USA). Her scientific interests in the Free Radical Research Group currently range from the in vitro antioxidant activity of single molecules to the modulation by natural antioxidants of oxidative dam- age, and apoptotic and proliferative response in cellular systems. Address correspondence to: Andrea Ghiselli, Free Radical Re- search Group, Istituto Nazionale di Ricerca su Alimenti e Nutrizione, 546 Via Ardeatina, 00178 Rome, Italy; Tel: +(39)065032412; Fax: +(39)065031592; E-Mail: ghiselli@inn.ingrm.it. Free Radical Biology & Medicine, Vol. 29, No. 11, pp. 1106 –1114, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0891-5849/00/$–see front matter PII S0891-5849(00)00394-4 1106