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Supplement: Free Radicals: The Pros and Cons of Antioxidants

Plasma Antioxidant Measurements¹

Arkansas Children’s Nutrition Center, Little Rock, AR 72202

²To whom correspondence should be addressed. E-mail: priorronaldl{at}uams.edu.

KEY WORDS: • antioxidant capacity • ORAC • oxidative stress

	EXPANDED ABSTRACT

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Measures of in vivo antioxidant status are important in understanding the role of oxidative events in the initiation and progression of numerous diseases, including cancer, atherosclerosis, and diabetes. In vivo antioxidant status can be assessed by measuring individual plasma or tissue levels of antioxidants such as vitamin C, vitamin E, or the carotenoids. However, the task is more difficult for numerous other compounds, including flavonoids and polyphenol-like compounds, that may influence in vivo antioxidant status. In these cases, measures of antioxidant capacity (AOC)³ are an important tool in the assessment of antioxidant status. Numerous techniques, often utilizing quite different free radical sources, are used to assess AOC in plasma. The radical sources used in the assay can, in some cases, have fairly dramatic effects on the antioxidant capacity observed because of the differential response of different types of antioxidant compounds to the specific radical source (1). Because of this variation, use of radical sources that are relevant to human biology becomes important in plasma analyses as well as in measures of AOC of foods. The peroxyl radical is the most common free radical in human biology, but the hydroxyl radical, singlet oxygen, superoxide radical, and reactive nitrogen species are all present in biological systems. Development of additional assays utilizing these radical and oxidant sources is needed to characterize relevant antioxidants (2). The utility of an antioxidant depends on the nature of the oxidant that inflicts tissue damage as well as the cellular component that is being attacked.

AOC is evaluated in terms of the levels of low-molecular-weight antioxidants in plasma or tissues. However, AOC assays do not address the role of various antioxidant enzymes in protecting against free radical action. Advantages of AOC measurements are that analysis of each of the individual antioxidant components is not necessary and an estimate of the total AOC can be obtained. However, until recently, a true measure of total antioxidant capacity (hydrophilic and lipophilic AOC) was not available. The Oxygen Radical Absorption Capacity (ORAC) assay was been adapted so that measures of both lipophilic and hydrophilic AOC can be obtained using the same peroxyl radical generator (2,3). Foods high in AOC can increase plasma AOC after a single meal (4). Although plasma AOC assays are useful, a complete panel of oxidative stress measures is needed to fully assess in vivo antioxidant status.

Clinical studies indicate that increased dietary intake of fruits and vegetables lowers oxidative stress (4) and that a high-fat diet is associated with increased oxidative stress. Some situations of oxidative stress may be such that dietary changes or antioxidant supplements in and of themselves may not correct or prevent the oxidative stress. Smoking in individuals with a low intake of fruits and vegetables is one example (5). Military training at moderate altitudes under cold temperatures may be another (6–8).

Future studies in this area should focus on three areas. The first is studies of the absorption and metabolism of antioxidant components in fruits and vegetables and their effect on in vivo antioxidant status. Knowledge of concentrations of antioxidants in foods is an important point from which to start; however, bioavailability and metabolism of food antioxidants will have a pronounced influence on the in vivo antioxidant response.

The second area is studies of the importance of antioxidant effects within the gastrointestinal (GI) tract. Diets rich in fruits and vegetables contain a complex mixture of antioxidants (including ascorbate, carotenoids, vitamin E, and other phenolics such as the flavonoids). However, the diet also may contain prooxidants, such as iron, copper, H₂O₂, and lipid peroxides. In considering the biological importance of dietary antioxidants, attention usually has focused on those that are absorbed through the GI tract into the rest of the body. The high levels of antioxidants present in certain foods (fruits, vegetables, grains) may play an important role in protecting the GI tract itself from oxidative damage and in delaying the development of cancer of the GI tract (i.e., esophageal, stomach, colon, and rectal). Prevention of the formation of lipid peroxides in the GI tract may be equally as important in preventing cardiovascular disease as oxidative events occurring within the vascular wall. Carotenoids and flavonoids (particularly anthocyanins and quercetin) (9) do not seem to be as well absorbed as vitamins C and E. Hence, their concentrations can be much higher in the lumen of the GI tract than ever are achieved in plasma or other body tissues, making an antioxidant action in the GI tract more likely (10).

Third, studies are needed to determine whether increased consumption, over an extended period of time, of foods with high levels of bioavailable AOC protect against free radical damage and subsequent development of disease. Until recently, no databases were available to evaluate dietary total antioxidant intake from nutrient as well as nonnutrient antioxidants such that relation to health outcomes might be established in epidemiological studies (11,12). The potential importance of such a technique was demonstrated recently. In evaluating the relation between dietary antioxidants and oxidative stress–induced diseases, an inverse correlation between total AOC intake and the risk of gastric cancer of both the cardia and distal portions of the stomach was found in a population-based case-control study (13). These relations were observed despite a very incomplete database of total AOC (only 12 items among fruits and vegetables).

	ACKNOWLEDGMENTS

 
The author thanks X. Wu and L. Gu for their suggestions and input.

	FOOTNOTES

 
¹ Presented as part of the conference "Free Radicals: The Pros and Cons of Antioxidants," held June 26–27 in Bethesda, MD. This conference was sponsored by the Division of Cancer Prevention (DCP) and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Department of Health and Human Services (DHHS); the National Center for Complementary and Alternative Medicine (NCCAM), NIH, DHHS; the Office of Dietary Supplements (ODS), NIH, DHHS; the American Society for Nutritional Science; and the American Institute for Cancer Research and supported by the DCP, NCCAM, and ODS. Guest editors for the supplement publication were Harold E. Seifried, National Cancer Institute, NIH; Barbara Sorkin, NCCAM, NIH; and Rebecca Costello, ODS, NIH.

³ Abbreviations used: AOC, antioxidant capacity; GI, gastrointestinal; ORAC, oxygen radical absorption capacity.

	LITERATURE CITED

TOP EXPANDED ABSTRACT LITERATURE CITED

 

1. Cao, G., Sofic, E. & Prior, R. L. (1996) Antioxidant capacity of tea and common vegetables. J. Agric. Food Chem. 44:3426-3431.

2. Huang, D., Ou, B., Hampsch-Woodill, M., Flanagan, J. & Deemer, E. (2002) Development and validation of oxygen radical absorbance capacity assay for lipophilic antioxidants using randomly methylated beta-cyclodextrin as the solubility enhancer. J. Agric. Food Chem. 50:1815-1821.[Medline]

3. Prior, R. L., Hoang, H., Gu, L., Wu, X., Bacchiocca, M., Howard, L., Hampsch-Woodill, M., Huang, D., Ou, B. & Jacob, R. (2003) Assays for hydrophilic and lipophilic antioxidant capacity (oxygen radical absorbance capacity (ORAC_FL)) of plasma and other biological and food samples. J. Agric. Food Chem. 51:3273-3279.[Medline]

4. Cao, G., Booth, S. L., Sadowski, J. A. & Prior, R. L. (1998) Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. Am. J. Clin. Nutr. 68:1081-1087.[Abstract]

5. van den Berg, R., van Vliet, T., Broekmans, W. M., Cnubben, N. H., Vaes, W. H., Roza, L., Haenen, G. R., Bast, A. & van den Berg, H. (2001) A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. J. Nutr. 131:1714-1722.[Abstract/Free Full Text]

6. Pfeiffer, J. M., Askew, E. W., Roberts, D. E., Wood, S. M., Benson, J. E., Johnson, S. C. & Freedman, M. S. (1999) Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training. Wilderness Environ. Med. 10:66-74.[Medline]

7. Chao, W. H., Askew, E. W., Roberts, D. E., Wood, S. M. & Perkins, J. B. (1999) Oxidative stress in humans during work at moderate altitude. J. Nutr. 129:2009-2012.[Abstract/Free Full Text]

8. Schmidt, M. C., Askew, E. W., Roberts, D. E., Prior, R. L., Ensign, W. Y., Jr & Hesslink, R. E., Jr (2002) Oxidative stress in humans training in a cold, moderate altitude environment and their response to a phytochemical antioxidant supplement. Wilderness Environ. Med. 13:94-105.[Medline]

9. Prior, R. L. (2003) Fruits and vegetables in the prevention of cellular oxidative damage. Am. J. Clin. Nutr. 78:570S-578S.[Abstract/Free Full Text]

10. Halliwell, B., Zhao, K. & Whiteman, M. (2000) The gastrointestinal tract: a major site of antioxidant action?. Free Radic. Res. 33:819-830.[Medline]

11. Wu, X., Gu, L., Holden, J., Haytowitz, D., Gebhardt, S., Beecher, G. & Prior, R. L. (2004) Factors in the development of a database of food total antioxidant capacity using lipophilic and hydrophilic oxygen radical absorbance capacity (ORAC_FL): A preliminary study of 28 foods. J. Food Compos. Anal. 17:407-422.

12. Wu, X., Beecher, G., Holden, J., Haytowitz, D., Gebhardt, S. & Prior, R. L. (2004) Lipophilic, hydrophilic antioxidant activities and total phenolics of foods: development of a food database. J. Agric Food Chem. 51(12):4026-4037.

13. Serafini, M., Bellocco, R., Wolk, A. & Ekstrom, A. M. (2002) Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology 123:985-991.[Medline]

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