Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention

Journal of the American College of Nutrition

Volumn 22, Issue 1, 2003, Pages 18-35

  Padayatty, Sebastian J ^a   Katz, Arie ^a   Wang, Yaohui ^a   Eck, Peter ^a   Kwon, Oran ^a   Lee, Je Hyuk ^a   Chen, Shenglin ^a   Corpe, Christopher ^a   Levine, Mark ^a   Dutta, Anand ^b   Dutta, Sudhir K ^b  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Ascorbic acid; Diet; Low density lipoproteins; Oxidation

Indexed keywords

ANTIOXIDANT; ASCORBIC ACID; BIOLOGICAL MARKER; LOW DENSITY LIPOPROTEIN;

CARDIOVASCULAR RISK; DIETARY INTAKE; ENZYMOLOGY; HUMAN; INGESTION; LIPID OXIDATION; OXIDATION; OXIDATIVE STRESS; PROTEIN SYNTHESIS; REVIEW; SURVIVAL; VASCULAR ENDOTHELIUM; VEGETABLE; VITAMIN INTAKE;

ANIMALS; ANTIOXIDANTS; ASCORBIC ACID; BIOLOGICAL AVAILABILITY; CARDIOVASCULAR DISEASES; DNA; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, DRUG; FRUIT; HUMANS; LIPID PEROXIDATION; NEOPLASMS; OXIDATION-REDUCTION; PROTEINS; VEGETABLES;

EID: 12244289625     PISSN: 07315724     EISSN: 15411087     Source Type: Journal    
DOI: 10.1080/07315724.2003.10719272     Document Type: Article

References (216)

1. Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K: Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for Lascorbic acid biosynthesis missing in man. J Biol Chem 269: 13685-13688, 1994.
2. Nishikimi M, Yagi K: Biochemistry and molecular biology of ascorbic acid biosynthesis. Subcell Biochem 25:17-39, 1996.
3. Buettner GR, Moseley PL: EPR spin trapping of free radicals produced by bleomycin and ascorbate. Free Radic Res Commun 19:S89-S93, 1993.
4. Bielski BH, Richter HW, Chan PC: Some properties of the ascorbate free radical. Ann N Y Acad Sci 258:231-237, 1975.
5. Washko PW, Wang Y, Levine M: Ascorbic acid recycling in human neutrophils. J Biol Chem 268:15531-15535, 1993.
6. Tolbert BM, Ward JB: Dehydroascorbic Acid. In Seib PA, Tolbert BM (eds): "Ascorbic Acid: Chemistry, Metabolism, and Uses." Washington, DC: American Chemical Society, pp 101-123, 1982.
7. Lewin S. "Vitamin C: Its Molecular Biology and Medical Potential." London: Academic Press, 1976.
8. Levine M, Rumsey SC, Wang Y, Park JB, Daruwala R. Vitamin C. In Stipanuk MH (ed): "Biochemical and Physiological Aspects of Human Nutrition." Philadelphia: W B Saunders, pp 541-567, 2000.
9. Prockop DJ, Kivirikko KI: Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 64:403-434, 1995.
10. Peterkofsky B: Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54:1135S-1140S, 1991.
11. Kivirikko KI, Myllyla R: Post-translational processing of procollagens. Ann N Y Acad Sci 460:187-201, 1985.
12. Rebouche CJ: Ascorbic acid and carnitine biosynthesis. Am J Clin Nutr 54:1147S-1152S, 1991.
13. Dunn WA, Rettura G, Seifter E, Englard S. Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gammabutyrobetaine hydroxylase. J Biol Chem 259:10764-10770, 1984.
14. Levine M, Dhariwal KR, Washko P, Welch R, Wang YH, Cantilena CC, Yu R: Ascorbic acid and reaction kinetics in situ: a new approach to vitamin requirements. J Nutr Sci Vitaminol (Tokyo) Spec No:169-172, 1992.
15. Kaufman S: Dopamine-beta-hydroxylase. J Psychiatr Res 11: 303-316, 1974.
16. Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE: Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains. Protein Sci 2:489-497, 1993.
17. Eipper BA, Stoffers DA, Mains RE: The biosynthesis of neuropeptides: peptide alpha-amidation. Annu Rev Neurosci 15:57-85, 1992.
18. Englard S, Seifter S: The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365-406, 1986.
19. Lindblad B, Lindstedt G, Lindstedt S: The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate. J Am Chem Soc 92:7446-7449, 1970.
20. Buettner GR: The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 300:535-543, 1993.
21. Halliwell B: Vitamin C: poison, prophylactic or panacea? Trends Biochem Sci 24:255-259, 1999.
22. Neuzil J, Thomas SR, Stocker R: Requirement for, promotion, or inhibition by alpha-tocopherol of radical-induced initiation of plasma lipoprotein lipid peroxidation. Free Radic Biol Med 22: 57-71, 1997.
23. Carr A, Frei B: Does vitamin C act as a pro-oxidant under physiological conditions? Faseb J 13:1007-1024, 1999.
24. Hallberg L: Iron and vitamins. Bibl Nutr Dieta 52:20-29, 1995.
25. Lynch SR: Interaction of iron with other nutrients. Nutr Rev 55:102-110, 1997.
26. Morrow JD: The isoprostanes: their quantification as an index of oxidant stress status in vivo. Drug Metab Rev 32:377-385, 2000.
27. Steinberg D: Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963-20966, 1997.
28. Heinecke JW: Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 141:1-15, 1998.
29. Witztum JL, Steinberg D: The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Trends Cardiovasc Med 11:93-102, 2001.
30. Berlett BS, Stadtman ER: Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272:20313-20316, 1997.
31. Shacter E: Quantification and significance of protein oxidation in biological samples. Drug Metab Rev 32:307-326, 2000.
32. Stadtman ER, Berlett BS: Reactive oxygen-mediated protein oxidation in aging and disease. Drug Metab Rev 30:225-243, 1998.
33. Baynes JW: The role of AGEs in aging: causation or correlation. Exp Gerontol 36:1527-1537, 2001.
34. Halliwell B: Why and how should we measure oxidative DNA damage in nutritional studies? How far have we come? Am J Clin Nutr 72:1082-1087, 2000.
35. Halliwell B: Vitamin C and genomic stability. Mutat Res 475: 29-35, 2001.
36. Lee SH, Oe T, Blair IA: Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science 292: 2083-2086, 2001.
37. Luperchio S, Tamir S, Tannenbaum SR: No-induced oxidative stress and glutathione metabolism in rodent and human cells. Free Radic Biol Med 21:513-519, 1996.
38. Odin AP: Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action. Mutat Res 386:39-67, 1997.
39. Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS, et al.: DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254:1001-1003, 1991.
40. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR: DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89: 3030-3034, 1992.
41. Haytowitz DB: Information from USDA's Nutrient Data Bank. J Nutr 125:1952-1955, 1995.
42. Lachance P, Langseth L: The RDA concept: time for a change? Nutr Rev 52:266-270, 1994.
43. Life Sciences Research Office: "Third Report on Nutrition Monitoring in the United States." Washington, DC: US Government Printing Office, 1995.
44. Simon JA, Schreiber GB, Crawford PB, Frederick MM, Sabry ZI: Dietary vitamin C and serum lipids in black and white girls. Epidemiology 4:537-542, 1993.
45. Basch CE, Zybert P, Shea S: 5-A-DAY: dietary behavior and the fruit and vegetable intake of Latino children. Am J Public Health 84:814-818, 1994.
46. Block G, Sinha R, Gridley G: Collection of dietary-supplement data and implications for analysis. Am J Clin Nutr 59:232S-239S, 1994.
47. Koplan JP, Annest JL, Layde PM, Rubin GL: Nutrient intake and supplementation in the United States (NHANES II). Am J Public Health 76:287-289, 1986.
48. Dickinson VA, Block G, Russek-Cohen E: Supplement use, other dietary and demographic variables, and serum vitamin C in NHANES II. J Am Coll Nutr 13:22-32, 1994.
49. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y: Criteria and recommendations for vitamin C intake. JAMA 281:1415-1423, 1999.
50. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR: Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 93:3704-3709, 1996.
51. Levine M, Wang Y, Padayatty SJ, Morrow J: A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci USA 98:9842-9846, 2001.
52. Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena Jr LR, Wang Y, Levine M: Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm Res 14:1133-1139, 1997.
53. Rumsey SC, Levine M: Absorption, transport, and disposition of ascorbic acid in humans. Nutritional Biochemistry 9:116-130, 1998.
54. Daruwala R, Song J, Koh WS, Rumsey SC, Levine M: Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCTFEBS Lett 460: 480-484, 1999.
55. Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen XZ, Wang Y, Brubaker RF, Hediger MA: A family of mammalian Na_-dependent L-ascorbic acid transporters. Nature 399:70-75, 1999.
56. Jialal I, Vega GL, Grundy SM: Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis 82:185-191, 1990.
57. Jialal I, Grundy SM: Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification. J Clin Invest 87:597-601, 1991.
58. Jialal I, Grundy SM: Influence of antioxidant vitamins on LDL oxidation. Ann N Y Acad Sci 669:237-247, 1992.
59. Jialal I, Fuller CJ: Effect of vitamin E, vitamin C and betacarotene on LDL oxidation and atherosclerosis. Can J Cardiol 11:97G-103G, 1995.
60. Frei B: Ascorbic acid protects lipids in human plasma and lowdensity lipoprotein against oxidative damage. Am J Clin Nutr 54:1113S-1118S, 1991.
61. Frei B, Gaziano JM: Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as predictors of the susceptibility of human LDL to metal ion-dependent and -independent oxidation. J Lipid Res 34:2135-2145, 1993.
62. Heinecke JW: Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall. Faseb J 13:1113-1120, 1999.
63. Crawford RS, Kirk EA, Rosenfeld ME, LeBoeuf RC, Chait A: Dietary antioxidants inhibit development of fatty streak lesions in the LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 18:1506-1513, 1998.
64. Heinecke JW: Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis. Arterioscler Thromb Vasc Biol 21:1261-1264, 2001.
65. Frei B, Stocker R, Ames BN: Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 85:9748-9752, 1988.
66. Frei B, England L, Ames BN: Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86: 6377-6381, 1989.
67. Lynch SM, Morrow JD, Roberts LJ, Frei B: Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J Clin Invest 93:998-1004, 1994.
68. Reilly M, Delanty N, Lawson JA, FitzGerald GA: Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 94:19-25, 1996.
69. Kim JG, Sabbagh F, Santanam N, Wilcox JN, Medford RM, Parthasarathy S: Generation of a polyclonal antibody against lipid peroxide-modified proteins. Free Radic Biol Med 23:251-259, 1997.
70. Eaton P, Hearse DJ, Shattock MJ: Lipid hydroperoxide modification of proteins during myocardial ischaemia. Cardiovasc Res 51:294-303, 2001.
71. Shanti A, Santanam N, Morales AJ, Parthasarathy S, Murphy AA: Autoantibodies to markers of oxidative stress are elevated in women with endometriosis. Fertil Steril 71:1115-1118, 1999.
72. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F: Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 21:844-848, 2001.
73. Holvoet P, Collen D: Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 137:S33-S38, 1998.
74. Hsu RM, Devaraj S, Jialal I: Autoantibodies to oxidized lowdensity lipoprotein in patients with Type 2 diabetes mellitus. Clin Chim Acta 317:145-150, 2002.
75. Barja G, Lopez-Torres M, Perez-Campo R, Rojas C, Cadenas S, Prat J, Pamplona R: Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. Free Radic Biol Med 17:105-115, 1994.
76. Kimura H, Yamada Y, Morita Y, Ikeda H, Matsuo T: Dietary ascorbic acid depresses plasma and low density lipoprotein lipid peroxidation in genetically scorbutic rats. J Nutr 122:1904-1909, 1992.
77. Tanaka K, Hashimoto T, Tokumaru S, Iguchi H, Kojo S: Interactions between vitamin C and vitamin E are observed in tissues of inherently scorbutic rats. J Nutr 127:2060-2064, 1997.
78. Cadenas S, Lertsiri S, Otsuka M, Barja G, Miyazawa T: Phospholipid hydroperoxides and lipid peroxidation in liver and plasma of ODS rats supplemented with alpha-tocopherol and ascorbic acid. Free Radic Res 24:485-493, 1996.
79. Kunert KJ, Tappel AL: The effect of vitamin C on in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production. Lipids 18:271-274, 1983.
80. Cadenas S, Rojas C, Barja G: Endotoxin increases oxidative injury to proteins in guinea pig liver: protection by dietary vitamin C. Pharmacol Toxicol 82:11-18, 1998.
81. Helen A, Vijayammal PL: Vitamin C supplementation on hepatic oxidative stress induced by cigarette smoke. J Appl Toxicol 17:289-295, 1997.
82. Dillard CJ, Kunert KJ, Tappel AL: Effects of vitamin E, ascorbic acid and mannitol on alloxan-induced lipid peroxidation in rats. Arch Biochem Biophys 216:204-212, 1982.
83. Kang SA, Jang YJ, Park H: In vivo dual effects of vitamin C on paraquat-induced lung damage: dependence on released metals from the damaged tissue. Free Radic Res 28:93-107, 1998.
84. Steinberg D, Lewis A: Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation 95:1062-1071, 1997.
85. Chisolm GM, Steinberg D: The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28:1815-1826, 2000.
86. Mahfouz MM, Kawano H, Kummerow FA: Effect of cholesterolrich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits. Am J Clin Nutr 66:1240-1249, 1997.
87. Halliwell B, Zhao K, Whiteman M: Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies. Free Radic Res 31:651-669, 1999.
88. Takahashi R, Goto S: Alteration of aminoacyl-tRNA synthetase with age: heat-labilization of the enzyme by oxidative damage. Arch Biochem Biophys 277:228-233, 1990.
89. Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER: Age-related changes in oxidized proteins. J Biol Chem 262:5488-5491, 1987.
90. Cross CE, O'Neill CA, Reznick AZ, Hu ML, Marcocci L, Packer L, Frei B: Cigarette smoke oxidation of human plasma constituents. Ann N Y Acad Sci 686:72-89, 1993.
91. Reznick AZ, Cross CE, Hu ML, Suzuki YJ, Khwaja S, Safadi A, Motchnik PA, Packer L, Halliwell B: Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation. Biochem J 286:607-611, 1992.
92. Yan LJ, Traber MG, Kobuchi H, Matsugo S, Tritschler HJ, Packer L: Efficacy of hypochlorous acid scavengers in the prevention of protein carbonyl formation. Arch Biochem Biophys 327:330-334, 1996.
93. Ortwerth BJ, James HL: Lens proteins block the copper-mediated formation of reactive oxygen species during glycation reactions in vitro. Biochem Biophys Res Commun 259:706-710, 1999.
94. Saxena P, Saxena AK, Cui XL, Obrenovich M, Gudipaty K, Monnier VM: Transition metal-catalyzed oxidation of ascorbate in human cataract extracts: possible role of advanced glycation end products. Invest Ophthalmol Vis Sci 41:1473-1481, 2000.
95. Cabiscol E, Levine RL: Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging. J Biol Chem 270:14742-14747, 1995.
96. Yan LJ, Sohal RS: Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 95:12896-12901, 1998.
97. Pennathur S, Wagner JD, Leeuwenburgh C, Litwak KN, Heinecke JW: A hydroxyl radical-like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease. J Clin Invest 107:853-860, 2001.
98. Frederikse PH, Garland D, Zigler Jr JS, Piatigorsky J: Oxidative stress increases production of beta-amyloid precursor protein and beta-amyloid (Abeta) in mammalian lenses, and Abeta has toxic effects on lens epithelial cells. J Biol Chem 271:10169-10174, 1996.
99. Fu S, Dean R, Southan M, Truscott R: The hydroxyl radical in lens nuclear cataractogenesis. J Biol Chem 273:28603-28609, 1998.
100. Taylor A, Smith DE, Palmer VJ, Shepard D, Padhye N, Theriault C, Morrow F: Relationships between acetone, cataracts, and ascorbate in hairless guinea pigs. Ophthalmic Research 25:30-35, 1993.
101. Taylor A: Nutritional influences on risk for cataract. Int Ophthalmol Clin 40:17-49, 2000.
102. Drouin R, Rodriguez H, Gao SW, Gebreyes Z, O'Connor TR, Holmquist GP, Akman SA: Cupric ion/ascorbate/hydrogen peroxide- induced DNA damage: DNA-bound copper ion primarily induces base modifications. Free Radic Biol Med 21:261-273, 1996.
103. Fischer-Nielsen A, Poulsen HE, Loft S: 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid. Free Radic Biol Med 13:121-216, 1992.
104. Hu ML, Shih MK: Ascorbic acid inhibits lipid peroxidation but enhances DNA damage in rat liver nuclei incubated with iron ions. Free Radic Res 26:585-592, 1997.
105. Singh NP: Sodium ascorbate induces DNA single-strand breaks in human cells in vitro. Mutat Res 375:195-203, 1997.
106. Ames BN: DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 475:7-20, 2001.
107. Cadenas S, Barja G, Poulsen HE, Loft S: Oxidative DNA damage estimated by oxo8dG in the liver of guinea-pigs supplemented with graded dietary doses of ascorbic acid and alpha-tocopherol. Carcinogenesis 18:2373-2377, 1997.
108. Reddy VN, Giblin FJ, Lin LR, Chakrapani B: The effect of aqueous humor ascorbate on ultraviolet-B-induced DNA damage in lens epithelium. Invest Ophthalmol Vis Sci 39:344-350, 1998.
109. Weimann A, Belling D, Poulsen HE: Quantification of 8-oxoguanine and guanine as the mucelobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry. Nucleic Acids Res 30:E7, 2002.
110. Tanaka K, Hayatsu T, Negishi T, Hayatsu H: Inhibition of Nnitrosation of secondary amines in vitro by tea extracts and catechins. Mutat Res 412:91-98, 1998.
111. Kessler H, Husemann B, Wagner W: Potential protective effect of vitamin C on carcinogenesis caused by nitrosamine in drinking water: an experimental study on Wistar rats. Eur J Surg Oncol 18:275-281, 1992.
112. Hagiwara A, Murai T, Yoshino H, Goshima H, Mori S, Takashima A, Shirai T, Fukushima S: Hepatocarcinogenic activity of N-butyl-N-(4-hydroxybutyl)nitrosamine in rats is not modified by sodium L-ascorbate. Teratog Carcinog Mutagen 19:33-42, 1999.
113. Chen T, Na Y, Wanibuchi H, Yamamoto S, Lee CC, Fukushima S: Loss of heterozygosity in (LewisxF344)F1 rat urinary bladder tumors induced with N-butyl-N-(4-hydroxybutyl)nitrosamine followed by dimethylarsinic acid or sodium L-ascorbate. Jpn J Cancer Res 90:818-823, 1999.
114. Haffner SM: Clinical relevance of the oxidative stress concept. Metabolism 49:30-34, 2000.
115. Baynes JW, Thorpe SR: Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 28:1708-1716, 2000.
116. Maxwell SR: Coronary artery disease-free radical damage, antioxidant protection and the role of homocysteine. Basic Res Cardiol 95(1):I65-I71, 2000.
117. Lipinski B: Pathophysiology of oxidative stress in diabetes mellitus. J Diabetes Complications 15:203-210, 2001.
118. Anderson JW, Gowri MS, Turner J, Nichols L, Diwadkar VA, Chow CK, Oeltgen PR: Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus. J Am Coll Nutr 18:451-461, 1999.
119. Ho E, Bray TM: Antioxidants, NFkappaB activation, and diabetogenesis. Proc Soc Exp Biol Med 222:205-213, 1999.
120. Cameron NE, Cotter MA: Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes 46(Suppl 2):S31- S37, 1997.
121. Miyata T, Kurokawa K, van Ypersele de Strihou C: Relevance of oxidative and carbonyl stress to long-term uremic complications. Kidney Int 58(76):S120-S125, 2000.
122. Descamps-Latscha B, Witko-Sarsat V: Importance of oxidatively modified proteins in chronic renal failure. Kidney Int 59(78):S108-S113, 2001.
123. Nguyen-Khoa T, Massy ZA, De Bandt JP, Kebede M, Salama L, Lambrey G, Witko-Sarsat V, Drueke TB, Lacour B, Thevenin M: Oxidative stress and haemodialysis: role of inflammation and duration of dialysis treatment. Nephrol Dial Transplant 16:335-340, 2001.
124. Blake DR, Winyard PG, Marok R: The contribution of hypoxiareperfusion injury to inflammatory synovitis: the influence of reactive oxygen intermediates on the transcriptional control of inflammation. Ann N Y Acad Sci 723:308-317, 1994.
125. Schulz HU, Niederau C, Klonowski-Stumpe H, Halangk W, Luthen R, Lippert H: Oxidative stress in acute pancreatitis. Hepatogastroenterology 46:2736-2750, 1999.
126. Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner- Felmayer G, Werner ER: L-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin. J Biol Chem 276:40-47, 2001.
127. Huang A, Vita JA, Venema RC, Keaney JF: Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 275:17399-17406, 2000.
128. Brown AA, Hu FB: Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr 73:673-686, 2001.
129. Drexler H, Hornig B: Endothelial dysfunction in human disease. J Mol Cell Cardiol 31:51-60, 1999.
130. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF, Vita JA: Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93: 1107-1113, 1996.
131. Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Yoshimura M, Ogawa H, Yasue H: Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C. Am J Physiol 273:H1644-H1650, 1997.
132. Beckman JA, Goldfine AB, Gordon MB, Creager MA: Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation 103:1618-1623, 2001.
133. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF: L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. J Clin Invest 101:1408-1414, 1998.
134. Jackson TS, Xu A, Vita JA, Keaney JF: Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res 83:916-922, 1998.
135. Duffy SJ, Gokce N, Holbrook M, Hunter LM, Biegelsen ES, Huang A, Keaney JF, Vita JA: Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension. Am J Physiol Heart Circ Physiol 280:H528-H534, 2001.
136. Padayatty SJ, Levine M: Vitamin C and coronary microcirculation. Circulation 103:E117, 2001.
137. Ness AR, Chee D, Elliott P: Vitamin C and blood pressure-an overview. J Hum Hypertens 11:343-350, 1997.
138. Bates CJ, Walmsley CM, Prentice A, Finch S: Does vitamin C reduce blood pressure? Results of a large study of people aged 65 or older. J Hypertens 16:925-932, 1998.
139. Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney JF, Vita JA: Treatment of hypertension with ascorbic acid. Lancet 354:2048-2049, 1999.
140. Fotherby MD, Williams JC, Forster LA, Craner P, Ferns GA: Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons. J Hypertens 18:411-415, 2000.
141. Bassenge E, Fink N, Skatchkov M, Fink B: Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest 102:67-71, 1998.
142. Hallberg L, Brune M, Rossander-Hulthen L: Is there a physiological role of vitamin C in iron absorption? Ann N Y Acad Sci 498:324-332, 1987.
143. Hallberg L: Wheat fiber, phytates and iron absorption. Scand J Gastroenterol Suppl 129:73-79, 1987.
144. Hallberg L, Brune M, Rossander L: The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl 30:103-108, 1989.
145. Davidsson L, Walczyk T, Morris A, Hurrell RF: Influence of ascorbic acid on iron absorption from an iron-fortified, chocolateflavored milk drink in Jamaican children. Am J Clin Nutr 67: 873-877, 1998.
146. Hunt JR, Mullen LM, Lykken GI, Gallagher SK, Nielsen FH: Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. Am J Clin Nutr 51:649-655, 1990.
147. Stack T, Aggett PJ, Aitken E, Lloyd DJ: Routine L-ascorbic acid supplementation does not alter iron, copper, and zinc balance in low-birth-weight infants fed a cows'-milk formula. J Pediatr Gastroenterol Nutr 10:351-356, 1990.
148. Harju E, Lindberg H: Ascorbic acid does not augment the restoration effect of iron treatment for empty iron stores in patients after gastrointestinal surgery. Am Surg 52:463-466, 1986.
149. Rhode BM, Shustik C, Christou NV, MacLean LD: Iron absorption and therapy after gastric bypass. Obes Surg 9:17-21, 1999.
150. Hunt JR, Gallagher SK, Johnson LK: Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 59:1381-1385, 1994.
151. Rathbone BJ, Johnson AW, Wyatt JI, Kelleher J, Heatley RV, Losowsky MS: Ascorbic acid: a factor concentrated in human gastric juice. Clin Sci 76:237-241, 1989.
152. Sobala GM, Schorah CJ, Sanderson M, Dixon MF, Tompkins DS, Godwin P, Axon AT: Ascorbic acid in the human stomach. Gastroenterology 97:357-363, 1989.
153. Sobala GM, Schorah CJ, Shires S, Lynch DA, Gallacher B, Dixon MF, Axon AT: Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations. Gut 34:1038-1041, 1993.
154. Sobala GM, Schorah CJ, Pignatelli B, Crabtree JE, Martin IG, Scott N, Quirke P: High gastric juice ascorbic acid concentrations in members of a gastric cancer family. Carcinogenesis 14:291-292, 1993.
155. Helser MA, Hotchkiss JH, Roe DA: Influence of fruit and vegetable juices on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid in humans on controlled diets. Carcinogenesis 13:2277-2280, 1992.
156. Byers T, Guerrero N: Epidemiologic evidence for vitamin C and vitamin E in cancer prevention. American Journal of Clinical Nutrition 62:1385S-1392S, 1995.
157. Ayaori M, Hisada T, Suzukawa M, Yoshida H, Nishiwaki M, Ito T, Nakajima K, Higashi K, Yonemura A, Ohsuzu F, Ishikawa T, Nakamura H: Plasma levels and redox status of ascorbic acid and levels of lipid peroxidation products in active and passive smokers. Environ Health Perspect 108:105-108, 2000.
158. Schectman G: Estimating ascorbic acid requirements for cigarette smokers. Ann N Y Acad Sci 686:335-345, discussion 345-346, 1993.
159. Stankova L, Riddle M, Larned J, Burry K, Menashe D, Hart J, Bigley R: Plasma ascorbate concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitus. Metabolism 33:347-353, 1984.
160. Will JC, Byers T: Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 54:193-202, 1996.
161. Sinclair AJ, Taylor PB, Lunec J, Girling AJ, Barnett AH: Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C. Diabet Med 11:893-898, 1994.
162. Hume R, Weyers E, Rowan T, Reid DS, Hillis WS: Leucocyte ascorbic acid levels after acute myocardial infarction. Br Heart J 34:238-243, 1972.
163. Riemersma RA, Carruthers KF, Elton RA, Fox KA: Vitamin C and the risk of acute myocardial infarction. Am J Clin Nutr 71:1181-1186, 2000.
164. Bonham MJ, Abu-Zidan FM, Simovic MO, Sluis KB, Wilkinson A, Winterbourn CC, Windsor JA: Early ascorbic acid depletion is related to the severity of acute pancreatitis. Br J Surg 86:1296-1301, 1999.
165. Scott P, Bruce C, Schofield D, Shiel N, Braganza JM, McCloy RF: Vitamin C status in patients with acute pancreatitis. Br J Surg 80:750-754, 1993.
166. Dallongeville J, Marecaux N, Fruchart JC, Amouyel P: Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis. J Nutr 128:1450-1457, 1998.
167. Padayatty SJ, Levine M: Vitamin C and myocardial infarction: the heart of the matter. Am J Clin Nutr 71:1027-1028, 2000.
168. Enstrom JE, Kanim LE, Klein MA: Vitamin C intake and mortality among a sample of the United States population. Epidemiology 3:194-202, 1992.
169. Gey KF: Cardiovascular disease and vitamins. Concurrent correction of 'suboptimal' plasma antioxidant levels may, as important part of 'optimal' nutrition, help to prevent early stages of cardiovascular disease and cancer, respectively. Bibl Nutr Dieta 52:75-91, 1995.
170. Kritchevsky SB, Shimakawa T, Tell GS, Dennis B, Carpenter M, Eckfeldt JH, Peacher-Ryan H, Heiss G: Dietary antioxidants and carotid artery wall thickness. The ARIC Study. Atherosclerosis Risk in Communities Study. Circulation 92:2142-2150, 1995.
171. Joshipura KJ, Ascherio A, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Hennekens CH, Spiegelman D, Willett WC: Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 282:1233-1239, 1999.
172. Ness AR, Powles JW: Fruit and vegetables, and cardiovascular disease: a review. Int J Epidemiol 26:1-13, 1997.
173. Daviglus ML, Orencia AJ, Dyer AR, Liu K, Morris DK, Persky V, Chavez N, Goldberg J, Drum M, Shekelle RB, Stamler J: Dietary vitamin C, beta-carotene and 30-year risk of stroke: results from the Western Electric Study. Neuroepidemiology 16: 69-77, 1997.
174. Gey KF, Moser UK, Jordan P, Stahelin HB, Eichholzer M, Ludin E: Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am J Clin Nutr 57:787S-797S, 1993.
175. Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Colditz G, Ascherio A, Rosner B, Spiegelman D, Willett WC: The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med 134:1106-1114, 2001.
176. Ascherio A, Rimm EB, Hernan MA, Giovannucci E, Kawachi I, Stampfer MJ, Willett WC: Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med 130:963-970, 1999.
177. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM: Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 334:1156-1162, 1996.
178. Ascherio A, Rimm EB, Hernan MA, Giovannucci E, Kawachi I, Stampfer MJ, Willett WC: Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med 130:963-970, 1999.
179. Hodis HN, Mack WJ, LaBree L, Cashin-Hemphill L, Sevanian A, Johnson R, Azen SP: Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 273:1849-1854, 1995.
180. Losonczy KG, Harris TB, Havlik RJ: Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr 64:190-106, 1996.
181. Mark SD, Wang W, Fraumeni Jr JF, Li JY, Taylor PR, Wang GQ, Guo W, Dawsey SM, Li B, Blot WJ: Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial. Am J Epidemiol 143:658-664, 1996.
182. Salonen JT, Nyyssonen K, Salonen R, Lakka HM, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, Tuomainen TP, Valkonen VP, Ristonmaa U, Poulsen HE: Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Intern Med 248:377-386, 2000.
183. Ness AR, Powles JW, Khaw KT: Vitamin C and cardiovascular disease: a systematic review. J Cardiovasc Risk 3:513-521, 1996.
184. Lonn EM, Yusuf S: Is there a role for antioxidant vitamins in the prevention of cardiovascular diseases? An update on epidemiological and clinical trials data. Can J Cardiol 13:957-965, 1997.
185. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S: The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 123:860-872, 1995.
186. Taylor A, Jacques PF, Chylack Jr LT, Hankinson SE, Khu PM, Rogers G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WC: Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. Am J Clin Nutr 75:540-549, 2002.
187. Chylack Jr LT, Brown NP, Bron A, Hurst M, Kopcke W, Thien U, Schalch W: The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiol 9:49-80, 2002.
188. Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. Arch Ophthalmol 119: 1439-1452, 2001.
189. Gale CR, Hall NF, Phillips DI, Martyn CN: Plasma antioxidant vitamins and carotenoids and age-related cataract. Ophthalmology 108:1992-1998, 2001.
190. Block G: Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr 54:1310S-1314S, 1991.
191. McCullough ML, Robertson AS, Jacobs EJ, Chao A, Calle EE, Thun MJ: A prospective study of diet and stomach cancer mortality in United States men and women. Cancer Epidemiol Biomarkers Prev 10:1201-1205, 2001.
192. Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, Manson JE, Hankinson SE, Willett WC: Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 91:547-556, 1999.
193. Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE, Willett WC: A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 329:234-240, 1993.
194. Hunter DJ, Colditz GA, Stampfer MJ, Rosner B, Willett WC, Speizer FE: Diet and risk of basal cell carcinoma of the skin in a prospective cohort of women. Ann Epidemiol 2:231-239, 1992.
195. Zhang SM, Hunter DJ, Rosner BA, Giovannucci EL, Colditz GA, Speizer FE, Willett WC: Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women. Cancer Epidemiol Biomarkers Prev 9:477-485, 2000.
196. Jacobs EJ, Connell CJ, Patel AV, Chao A, Rodriguez C, Seymour J, McCullough ML, Calle EE, Thun MJ: Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort. Cancer Epidemiol Biomarkers Prev 10:17-23, 2001.
197. Greenberg ER, Baron JA, Tosteson TD, Freeman Jr DH, Beck GJ, Bond JH, Colacchio TA, Coller JA, Frankl HD, Haile RW, et al.: A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med 331: 141-147, 1994.
198. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey SM, Li B: The Linxian trials: mortality rates by vitamin-mineral intervention group. Am J Clin Nutr 62:1424S-1426S, 1995.
199. Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K: Which plasma antioxidants are most related to fruit and vegetable consumption? Am J Epidemiol 154:1113-1118, 2001.
200. Food and Nutrition Board: "Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids: A Report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine." Washington, DC: National Academy Press, pp 95-184, 2000.
201. Pratico D: F(2)-isoprostanes: sensitive and specific non-invasive indices of lipid peroxidation in vivo. Atherosclerosis 147:1-10, 1999.
202. Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts 2nd LJ: Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med 332: 1198-1203, 1995.
203. Steinberg FM, Chait A: Antioxidant vitamin supplementation and lipid peroxidation in smokers. Am J Clin Nutr 68:319-327, 1998.
204. Porkkala-Sarataho E, Salonen JT, Nyyssonen K, Kaikkonen J, Salonen R, Ristonmaa U, Diczfalusy U, Brigelius-Flohe R, Loft S, Poulsen HE: Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2b- deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. Arterioscler Thromb Vasc Biol 20:2087-2093, 2000.
205. Dietrich M, Block G, Hudes M, Morrow JD, Norkus EP, Traber MG, Cross CE, Packer L: Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. Cancer Epidemiol Biomarkers Prev 11:7-13, 2002.
206. Chevion M, Berenshtein E, Stadtman ER: Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 33:S99-S108, 2000.
207. Carty JL, Bevan R, Waller H, Mistry N, Cooke M, Lunec J, Griffiths HR: The effects of vitamin C supplementation on protein oxidation in healthy volunteers. Biochem Biophys Res Commun 273:729-735, 2000.
208. Daube H, Scherer G, Riedel K, Ruppert T, Tricker AR, Rosenbaum P, Adlkofer F: DNA adducts in human placenta in relation to tobacco smoke exposure and plasma antioxidant status. J Cancer Res Clin Oncol 123:141-151, 1997.
209. Huang HY, Helzlsouer KJ, Appel LJ: The effects of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 9:647- 652, 2000.
210. Jacobson JS, Begg MD, Wang LW, Wang Q, Agarwal M, Norkus E, Singh VN, Young TL, Yang D, Santella RM: Effects of a 6-month vitamin intervention on DNA damage in heavy smokers. Cancer Epidemiol Biomarkers Prev 9:1303-1311, 2000.
211. Lee BM, Lee SK, Kim HS: Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng). Cancer Lett 132:219-227, 1998.
212. Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J: Vitamin C exhibits prooxidant properties. Nature 392: 559, 1998.
213. van den Berg R, van Vliet T, Broekmans WM, Cnubben NH, Vaes WH, Roza L, Haenen GR, Bast A, van den Berg H: A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. J Nutr 131:1714-1722, 2001.
214. van't Veer PV, Kok FJ: Human studies to substantiate health effects of antioxidants. What is needed? Free Radic Res 33:S109- S115, 2000.
215. Boaz M, Green M, Fainauru M, Smetana S: Oxidative stress and cardiovascular disease in hemodialysis. Clin Nephrol 55:93-100, 2001.
216. Weinstein T, Chagnac A, Korzets A, Boaz M, Ori Y, Herman M, Malachi T, Gafter U: Haemolysis in haemodialysis patients: evidence for impaired defence mechanisms against oxidative stress. Nephrol Dial Transplant 15:883-887, 2000.