Antioxidants

Abstract

In the human body, antioxidant functions (elimination of excessive reactive oxygen species (ROS)) are primarily exerted by enzyme systems in cells and tissues or by antioxidant molecules produced by metabolism. A large number of molecules, chemically defined as antioxidants, present in fruits and vegetables (polyphenols, tocopherols and carotenoids) are provided with the property of delaying or inhibiting oxidations. They can exhibit additional functions such as of ligands to macromolecules (receptors, enzymes, etc.). The in vitro properties of antioxidants may not be present in vivo, if the antioxidant is not absorbed, or if it is modified, if it is inactivated or rapidly eliminated. Antioxidants may scavenge ROS in excess that can damage cell components, such as deoxyribonucleic acid, proteins, lipids and low‐molecular weight compounds. However, because ROS represent physiological components of cell metabolism and are used for cell signalling, antioxidants may interfere with physiological cell signalling. Although epidemiological studies have suggested a positive health impact of antioxidants present in fruits and vegetables, human interventions with antioxidants have not given till now encouraging results.

Key Concepts:

  • Antioxidants are a broad, heterogeneous group of chemicals provided with the property delaying or inhibiting oxidations.

  • Antioxidant functions are also exerted by enzyme systems, physiologically present in cells and tissues.

  • Antioxidants may possess properties additional to their redox reactivity.

  • A clear distinction should be made between in vitro and in vivo properties of antioxidants, because in vivo chemical antioxidants may be inactivated, modified or exhibit different, additional properties.

  • Reactive oxygen species are present as physiological components of cell metabolism and are used for cell signalling.

  • Reactive oxygen species in excess can damage cell components, such as DNA, proteins, lipids and low‐molecular weight compounds, and be the cause of disease.

  • Antioxidants may on one side prevent the damage produced by excess oxidants, but they may also interfere with the physiological signalling produced by reactive oxygen species.

  • Epidemiological studies have suggested a positive health impact of antioxidants present in fruits and vegetables.

  • Human interventions with antioxidants have not given till now encouraging results.

Keywords: antioxidants; signalling; tocopherol; free radicals; reactive oxygen species

Figure 1.

Polyphenols: general structure.

Figure 2.

Beta‐carotene.

Figure 3.

Alpha‐tocopherol.

close

References

Atkinson J, Epand RF and Epand RM (2008) Tocopherols and tocotrienols in membranes: a critical review. Free Radical Biology & Medicine 44(5): 739–764.

Azzi A (2007) Molecular mechanism of alpha‐tocopherol action. Free Radical Biology & Medicine 43(1): 16–21.

van den Berg R, van Vliet T, Broekmans WM et al. (2001) A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. Journal of Nutrition 131(6): 1714–1722.

Bjelakovic G, Nikolova D, Gluud LL et al. (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta‐analysis. Journal of the American Medical Association 297(8): 842–857.

Britton G (1995) Structure and properties of carotenoids in relation to function. Faseb Journal 9(15): 1551–1558.

Cachia O, Benna JE, Pedruzzi E et al. (1998) Alpha‐tocopherol inhibits the respiratory burst in human monocytes. Attenuation of p47(phox) membrane translocation and phosphorylation. Journal of Biological Chemistry 273(49): 32801–32805.

Cadenas E and Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radical Biology & Medicine 29(3–4): 222–230.

Cleveland C (2010) Heart and Vascular Health & Prevention. Available at http://my.clevelandclinic.org/heart/disorders/cad/vitamin_e.aspx (accessed on 30 December, 2010).

Das S, Lekli I, Das M et al. (2008) Cardioprotection with palm oil tocotrienols: comparison of different isomers. American Journal of Physiology. Heart and Circulatory Physiology 294(2): H970–H978.

Dasgupta B and Milbrandt J (2007) Resveratrol stimulates AMP kinase activity in neurons. Proceedings of the National Academy of Sciences of the USA 104(17): 7217–7222.

Droge W (2002) Free radicals in the physiological control of cell function. Physiological Reviews 82(1): 47–95.

Duester G (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134(6): 921–931.

Ejaz A, Wu D, Kwan P et al. (2009) Curcumin inhibits adipogenesis in 3T3‐L1 adipocytes and angiogenesis and obesity in C57/BL mice. Journal of Nutrition 139(5): 919–925.

Evans J (2008) Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and meta‐analysis. Eye (London) 22(6): 751–760.

Fita I and Rossmann MG (1985) The active center of catalase. Journal of Molecular Biology 185(1): 21–37.

Gomez‐Cabrera MC, Domenech E, Romagnoli M et al. (2008) Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training‐induced adaptations in endurance performance. American Journal of Clinical Nutrition 87(1): 142–149.

Greenberg ER, Baron JA, Tosteson TD et al. (1994) A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. New England Journal of Medicine 331(3): 141–147.

Harborne JB (1988) Flavonoids in the environment: structure‐activity relationships. Progress in Clinical and Biological Research 280: 17–27.

Iuliano L, Micheletta F, Maranghi M et al. (2001) Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide‐scavenging activity and cholesterol‐oxidation products. Arteriosclerosis, Thrombosis, and Vascular Biology 21(10): E34–E37.

Knutson MD and Leeuwenburgh C (2008) Resveratrol and novel potent activators of SIRT1: effects on aging and age‐related diseases. Nutrition Reviews 66(10): 591–596.

Krinsky NI (1998) The antioxidant and biological properties of the carotenoids. Annals of the New York Academy of Sciences 854: 443–447.

Lambert JD, Sang S and Yang CS (2007) Possible controversy over dietary polyphenols: benefits vs risks. Chemical Research in Toxicology 20(4): 583–585.

Lee IM, Cook NR, Gaziano JM et al. (2005) Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. Journal of the American Medical Association 294(1): 56–65.

Li HL, Huang Y, Zhang CN et al. (2006) Epigallocathechin‐3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species‐dependent and ‐independent signal pathways. Free Radical Biology & Medicine 40(10): 1756–1775.

Loschen G, Azzi A, Richter C et al. (1974) Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Letters 42(1): 68–72.

Lotito SB and Frei B (2004) The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple‐derived antioxidant flavonoids. Free Radical Biology & Medicine 37(2): 251–258.

Meister A (1994) Glutathione‐ascorbic acid antioxidant system in animals. Journal of Biological Chemistry 269(13): 9397–9400.

Miller ER 3rd, Pastor‐Barriuso R, Dalal D et al. (2005) Meta‐analysis: high‐dosage vitamin E supplementation may increase all‐cause mortality. Annals of Internal Medicine 142(1): 37–46.

Miller NJ, Sampson J, Candeias LP et al. (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Letters 384(3): 240–242.

Negis Y, Zingg JM, Libinaki R et al. (2009) Vitamin E and cancer. Nutrition and Cancer 61(6): 875–878.

Nielsen IL and Williamson G (2007) Review of the factors affecting bioavailability of soy isoflavones in humans. Nutrition and Cancer 57(1): 1–10.

Peake JM, Suzuki K and Coombes JS (2007) The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise. Journal of Nutritional Biochemistry 18(6): 357–371.

Pirola L and Frojdo S (2008) Resveratrol: one molecule, many targets. IUBMB Life 60(5): 323–332.

Rhee SG (2006) Cell signaling. H2O2, a necessary evil for cell signaling. Science 312(5782): 1882–1883.

Rigotti A (2007) Absorption, transport, and tissue delivery of vitamin E. Molecular Aspects of Medicine 28(5–6): 423–436.

Rimm EB, Stampfer MJ, Ascherio A et al. (1993) Vitamin E consumption and the risk of coronary heart disease in men. New England Journal of Medicine 328(20): 1450–1456.

Scalbert A and Williamson G (2000) Dietary intake and bioavailability of polyphenols. Journal of Nutrition 130(8S suppl): 2073S–2085S.

Schroeter H, Heiss C, Balzer J et al. (2006) (‐)‐Epicatechin mediates beneficial effects of flavanol‐rich cocoa on vascular function in humans. Proceedings of the National Academy of Sciences of the USA 103(4): 1024–1029.

Sen CK, Khanna S and Roy S (2006) Tocotrienols: vitamin E beyond tocopherols. Life Sciences 78(18): 2088–2098.

Sies H (1993) Strategies of antioxidant defense. European Journal of Biochemistry 215(2): 213–219.

Sies H (2010) Polyphenols and health: update and perspectives. Archives of Biochemistry and Biophysics 501(1): 2–5.

Smirnoff N and Wheeler GL (2000) Ascorbic acid in plants: biosynthesis and function. Critical Reviews in Biochemistry and Molecular Biology 35(4): 291–314.

Stanner SA, Hughes J, Kelly CN et al. (2004) A review of the epidemiological evidence for the ‘antioxidant hypothesis’. Public Health Nutrition 7(3): 407–422.

Tanvetyanon T and Bepler G (2008) Beta‐carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta‐analysis and evaluation of national brands. Cancer 113(1): 150–157.

Turrens JF (2003) Mitochondrial formation of reactive oxygen species. Journal of Physiology 552(part 2): 335–344.

Williams MD, Van Remmen H, Conrad CC et al. (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. Journal of Biological Chemistry 273(43): 28510–28515.

Williamson G and Manach C (2005) Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. American Journal of Clinical Nutrition 81(1 suppl): 243S–255S.

Williamson G, Sies H, Heber D et al. (2009) Functional foods for health promotion: state‐of‐the‐science on dietary flavonoids. Extended abstracts from the 12th Annual Conference on Functional Foods for Health Promotion, April 2009. Nutrition Reviews 67(12): 736–743.

Winyard PG, Moody CJ and Jacob C (2005) Oxidative activation of antioxidant defence. Trends in Biochemical Science 30(8): 453–461.

Zhang P and Omaye ST (2001) Antioxidant and prooxidant roles for beta‐carotene, alpha‐tocopherol and ascorbic acid in human lung cells. Toxicology In vitro 15(1): 13–24.

Further Reading

Bedard K and Krause KH (2007) The NOX family of ROS‐generating NADPH oxidases: physiology and pathophysiology. Physiological Reviews 87(1): 245–313.

Fraga CC (2010) Plant Phenolics and Human Health. Hoboken, NJ: Wiley.

Imlay JA (2008) Cellular defenses against superoxide and hydrogen peroxide. Annual Review of Biochemistry 77: 755–776.

Johnson F and Giulivi C (2005) Superoxide dismutases and their impact upon human health. Molecular Aspects of Medicine 26: 340–352.

Luciano Pirola (2010) BioFactors. Special Issue on “Resveratrol” 36(5): 329–406.

Panel on Dietary Antioxidants and Related Compounds (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Dugo, Laura, Negis, Yesim, and Azzi, Angelo(Feb 2011) Antioxidants. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023204]