8,675
Views
1,167
CrossRef citations to date
0
Altmetric
Review Series: Antioxidants and Their Clinical Applications

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

, MRCP, PhD, , MD, , MD, , PhD, , PhD, , PhD, , PhD, , PhD, , BS, , MD, FACN & , MD, FACN show all
Pages 18-35 | Received 12 Apr 2002, Accepted 13 May 2002, Published online: 19 Jun 2013

  • 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 L-ascorbic acid biosynthesis missing in man.J Biol Chem269 :13685– 13688,1994 .
  • Nishikimi M, Yagi K: Biochemistry and molecular biology of ascorbic acid biosynthesis.Subcell Biochem25 :17– 39,1996 .
  • Buettner GR, Moseley PL: EPR spin trapping of free radicals produced by bleomycin and ascorbate.Free Radic Res Commun19 :S89– S93,1993 .
  • Bielski BH, Richter HW, Chan PC: Some properties of the ascorbate free radical.Ann N Y Acad Sci258 :231– 237,1975 .
  • Washko PW, Wang Y, Levine M: Ascorbic acid recycling in human neutrophils.J Biol Chem268 :15531– 15535,1993 .
  • Tolbert BM, Ward JB: Dehydroascorbic Acid. In Seib PA, Tolbert BM (eds):“Ascorbic Acid: Chemistry, Metabolism, and Uses.” Washington, DC: American Chemical Society, pp101– 123,1982 .
  • Lewin S.“Vitamin C: Its Molecular Biology and Medical Potential.” London: Academic Press,1976 .
  • 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, pp541– 567,2000 .
  • Prockop DJ, Kivirikko KI: Collagens: molecular biology, diseases, and potentials for therapy.Annu Rev Biochem64 :403– 434,1995 .
  • Peterkofsky B: Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy.Am J Clin Nutr54 :1135S– 1140S,1991 .
  • Kivirikko KI, Myllyla R: Post-translational processing of procollagens.Ann N Y Acad Sci460 :187– 201,1985 .
  • Rebouche CJ: Ascorbic acid and carnitine biosynthesis.Am J Clin Nutr54 :1147S– 1152S,1991 .
  • 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 gamma-butyrobetaine hydroxylase.J Biol Chem259 :10764– 10770,1984 .
  • 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 .
  • Kaufman S: Dopamine-beta-hydroxylase.J PsychiatrRes 11 :303– 316,1974 .
  • Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE: Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains.Protein Sci2 :489– 497,1993 .
  • Eipper BA, Stoffers DA, Mains RE: The biosynthesis of neuropeptides: peptide alpha-amidation.Annu Rev Neurosci15 :57– 85,1992 .
  • Englard S, Seifter S: The biochemical functions of ascorbic acid.Annu Rev Nutr6 :365– 406,1986 .
  • Lindblad B, Lindstedt G, Lindstedt S: The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate.J Am Chem Soc92 :7446– 7449,1970 .
  • Buettner GR: The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate.Arch Biochem Biophys300 :535– 543,1993 .
  • Halliwell B: Vitamin C: poison, prophylactic or panacea?Trends Biochem Sci24 :255– 259,1999 .
  • 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 Med22 :57– 71,1997 .
  • Carr A, Frei B: Does vitamin C act as a pro-oxidant under physiological conditions?Faseb J13 :1007– 1024,1999 .
  • Hallberg L: Iron and vitamins.Bibl Nutr Dieta52 :20– 29,1995 .
  • Lynch SR: Interaction of iron with other nutrients.Nutr Rev55 :102– 110,1997 .
  • Morrow JD: The isoprostanes: their quantification as an index of oxidant stress status in vivo.Drug Metab Rev32 :377– 385,2000 .
  • Steinberg D: Low density lipoprotein oxidation and its pathobiological significance.J Biol Chem272 :20963– 20966,1997 .
  • Heinecke JW: Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis.Atherosclerosis141 :1– 15,1998 .
  • Witztum JL, Steinberg D: The oxidative modification hypothesis of atherosclerosis: does it hold for humans?Trends Cardiovasc Med11 :93– 102,2001 .
  • Berlett BS, Stadtman ER: Protein oxidation in aging, disease, and oxidative stress.J Biol Chem272 :20313– 20316,1997 .
  • Shacter E: Quantification and significance of protein oxidation in biological samples.Drug Metab Rev32 :307– 326,2000 .
  • Stadtman ER, Berlett BS: Reactive oxygen-mediated protein oxidation in aging and disease.Drug Metab Rev30 :225– 243,1998 .
  • Baynes JW: The role of AGEs in aging: causation or correlation.Exp Gerontol36 :1527– 1537,2001 .
  • Halliwell B: Why and how should we measure oxidative DNA damage in nutritional studies? How far have we come?Am J Clin Nutr72 :1082– 1087,2000 .
  • Halliwell B: Vitamin C and genomic stability.Mutat Res475 :29– 35,2001 .
  • Lee SH, Oe T, Blair IA: Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins.Science292 :2083– 2086,2001 .
  • Luperchio S, Tamir S, Tannenbaum SR: No-induced oxidative stress and glutathione metabolism in rodent and human cells.Free Radic Biol Med21 :513– 519,1996 .
  • Odin AP: Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action.Mutat Res386 :39– 67,1997 .
  • 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.Science254 :1001– 1003,1991 .
  • 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 USA89 :3030– 3034,1992 .
  • Haytowitz DB: Information from USDA’s Nutrient Data Bank.J Nutr125 :1952– 1955,1995 .
  • Lachance P, Langseth L: The RDA concept: time for a change?Nutr Rev52 :266– 270,1994 .
  • Life Sciences Research Office:“Third Report on Nutrition Monitoring in the United States.” Washington, DC: US Government Printing Office,1995 .
  • Simon JA, Schreiber GB, Crawford PB, Frederick MM, Sabry ZI: Dietary vitamin C and serum lipids in black and white girls.Epidemiology4 :537– 542,1993 .
  • Basch CE, Zybert P, Shea S: 5-A-DAY: dietary behavior and the fruit and vegetable intake of Latino children.Am J Public Health84 :814– 818,1994 .
  • Block G, Sinha R, Gridley G: Collection of dietary-supplement data and implications for analysis.Am J Clin Nutr59 :232S– 239S,1994 .
  • Koplan JP, Annest JL, Layde PM, Rubin GL: Nutrient intake and supplementation in the United States (NHANES II).Am J Public Health76 :287– 289,1986 .
  • Dickinson VA, Block G, Russek-Cohen E: Supplement use, other dietary and demographic variables, and serum vitamin C in NHANES II.J Am Coll Nutr13 :22– 32,1994 .
  • Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y: Criteria and recommendations for vitamin C intake.JAMA281 :1415– 1423,1999 .
  • 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 USA93 :3704– 3709,1996 .
  • Levine M, Wang Y, Padayatty SJ, Morrow J: A new recommended dietary allowance of vitamin C for healthy young women.Proc Natl Acad Sci USA98 :9842– 9846,2001 .
  • 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 Res14 :1133– 1139,1997 .
  • Rumsey SC, Levine M: Absorption, transport, and disposition of ascorbic acid in humans.Nutritional Biochemistry9 :116– 130,1998 .
  • Daruwala R, Song J, Koh WS, Rumsey SC, Levine M: Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2.FEBS Lett460 :480– 484,1999 .
  • 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.Nature399 :70– 75,1999 .
  • Jialal I, Vega GL, Grundy SM: Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein.Atherosclerosis82 :185– 191,1990 .
  • Jialal I, Grundy SM: Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification.J Clin Invest87 :597– 601,1991 .
  • Jialal I, Grundy SM: Influence of antioxidant vitamins on LDL oxidation.Ann N Y Acad Sci669 :237– 247,1992 .
  • Jialal I, Fuller CJ: Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and atherosclerosis.Can J Cardiol11 :97G– 103G,1995 .
  • Frei B: Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage.Am J Clin Nutr54 :1113S– 1118S,1991 .
  • 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 Res34 :2135– 2145,1993 .
  • 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 J13 :1113– 1120,1999 .
  • 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 Biol18 :1506– 1513,1998 .
  • Heinecke JW: Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis.Arterioscler Thromb Vasc Biol21 :1261– 1264,2001 .
  • Frei B, Stocker R, Ames BN: Antioxidant defenses and lipid peroxidation in human blood plasma.Proc Natl Acad Sci USA85 :9748– 9752,1988 .
  • Frei B, England L, Ames BN: Ascorbate is an outstanding antioxidant in human blood plasma.Proc Natl Acad Sci USA86 :6377– 6381,1989 .
  • Lynch SM, Morrow JD, Roberts 2nd 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 Invest93 :998– 1004,1994 .
  • Reilly M, Delanty N, Lawson JA, FitzGerald GA: Modulation of oxidant stress in vivo in chronic cigarette smokers.Circulation94 :19– 25,1996 .
  • 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 Med23 :251– 259,1997 .
  • Eaton P, Hearse DJ, Shattock MJ: Lipid hydroperoxide modification of proteins during myocardial ischaemia.Cardiovasc Res51 :294– 303,2001 .
  • Shanti A, Santanam N, Morales AJ, Parthasarathy S, Murphy AA: Autoantibodies to markers of oxidative stress are elevated in women with endometriosis.Fertil Steril71 :1115– 1118,1999 .
  • 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 Biol21 :844– 848,2001 .
  • Holvoet P, Collen D: Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis.Atherosclerosis137(Suppl) :S33– S38,1998 .
  • Hsu RM, Devaraj S, Jialal I: Autoantibodies to oxidized low-density lipoprotein in patients with Type 2 diabetes mellitus.Clin Chim Acta317 :145– 150,2002 .
  • 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 Med17 :105– 115,1994 .
  • 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 Nutr122 :1904– 1909,1992 .
  • 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 Nutr127 :2060– 2064,1997 .
  • 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 Res24 :485– 493,1996 .
  • Kunert KJ, Tappel AL: The effect of vitamin C on in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production.Lipids18 :271– 274,1983 .
  • Cadenas S, Rojas C, Barja G: Endotoxin increases oxidative injury to proteins in guinea pig liver: protection by dietary vitamin C.Pharmacol Toxicol82 :11– 18,1998 .
  • Helen A, Vijayammal PL: Vitamin C supplementation on hepatic oxidative stress induced by cigarette smoke.J Appl Toxicol17 :289– 295,1997 .
  • Dillard CJ, Kunert KJ, Tappel AL: Effects of vitamin E, ascorbic acid and mannitol on alloxan-induced lipid peroxidation in rats.Arch Biochem Biophys216 :204– 212,1982 .
  • 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 Res28 :93– 107,1998 .
  • Steinberg D, Lewis A: Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis.Circulation95 :1062– 1071,1997 .
  • Chisolm GM, Steinberg D: The oxidative modification hypothesis of atherogenesis: an overview.Free Radic Biol Med28 :1815– 1826,2000 .
  • Mahfouz MM, Kawano H, Kummerow FA: Effect of cholesterol-rich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits.Am J Clin Nutr66 :1240– 1249,1997 .
  • 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 Res31 :651– 669,1999 .
  • Takahashi R, Goto S: Alteration of aminoacyl-tRNA synthetase with age: heat-labilization of the enzyme by oxidative damage.Arch Biochem Biophys277 :228– 233,1990 .
  • Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER: Age-related changes in oxidized proteins.J Biol Chem262 :5488– 5491,1987 .
  • 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 Sci686 :72– 89,1993 .
  • 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 J286 :607– 611,1992 .
  • 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 Biophys327 :330– 334,1996 .
  • Ortwerth BJ, James HL: Lens proteins block the copper-mediated formation of reactive oxygen species during glycation reactions in vitro.Biochem Biophys Res Commun259 :706– 710,1999 .
  • 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 Sci41 :1473– 1481,2000 .
  • Cabiscol E, Levine RL: Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging.J Biol Chem270 :14742– 14747,1995 .
  • Yan LJ, Sohal RS: Mitochondrial adenine nucleotide translocase is modified oxidatively during aging.Proc Natl Acad Sci USA95 :12896– 12901,1998 .
  • 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 Invest107 :853– 860,2001 .
  • 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 Chem271 :10169– 10174,1996 .
  • Fu S, Dean R, Southan M, Truscott R: The hydroxyl radical in lens nuclear cataractogenesis.J Biol Chem273 :28603– 28609,1998 .
  • 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 Research25 :30– 35,1993 .
  • Taylor A: Nutritional influences on risk for cataract.Int Ophthalmol Clin40 :17– 49,2000 .
  • 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 Med21 :261– 273,1996 .
  • Fischer-Nielsen A, Poulsen HE, Loft S: 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid.Free Radic Biol Med13 :121– 216,1992 .
  • Hu ML, Shih MK: Ascorbic acid inhibits lipid peroxidation but enhances DNA damage in rat liver nuclei incubated with iron ions.Free Radic Res26 :585– 592,1997 .
  • Singh NP: Sodium ascorbate induces DNA single-strand breaks in human cells in vitro.Mutat Res375 :195– 203,1997 .
  • Ames BN: DNA damage from micronutrient deficiencies is likely to be a major cause of cancer.Mutat Res475 :7– 20,2001 .
  • 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.Carcinogenesis18 :2373– 2377,1997 .
  • 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 Sci39 :344– 350,1998 .
  • Weimann A, Belling D, Poulsen HE: Quantification of 8-oxo-guanine and guanine as the mucelobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry.Nucleic Acids Res30 :E7 ,2002 .
  • Tanaka K, Hayatsu T, Negishi T, Hayatsu H: Inhibition of N-nitrosation of secondary amines in vitro by tea extracts and catechins.Mutat Res412 :91– 98,1998 .
  • 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 Oncol18 :275– 281,1992 .
  • 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 Mutagen19 :33– 42,1999 .
  • 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 Res90 :818– 823,1999 .
  • Haffner SM: Clinical relevance of the oxidative stress concept.Metabolism49 :30– 34,2000 .
  • Baynes JW, Thorpe SR: Glycoxidation and lipoxidation in atherogenesis.Free Radic Biol Med28 :1708– 1716,2000 .
  • Maxwell SR: Coronary artery disease-free radical damage, antioxidant protection and the role of homocysteine.Basic Res Cardiol95(Suppl 1) :I65– I71,2000 .
  • Lipinski B: Pathophysiology of oxidative stress in diabetes mellitus.J Diabetes Complications15 :203– 210,2001 .
  • 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 Nutr18 :451– 461,1999 .
  • Ho E, Bray TM: Antioxidants, NFkappaB activation, and diabetogenesis.Proc Soc Exp Biol Med222 :205– 213,1999 .
  • Cameron NE, Cotter MA: Metabolic and vascular factors in the pathogenesis of diabetic neuropathy.Diabetes 46(Suppl2) :S31– S37,1997 .
  • Miyata T, Kurokawa K, van Ypersele de Strihou C: Relevance of oxidative and carbonyl stress to long-term uremic complications.Kidney Int 58(Suppl76) :S120– S125,2000 .
  • Descamps-Latscha B, Witko-Sarsat V: Importance of oxidatively modified proteins in chronic renal failure.Kidney Int59(Suppl 78) :S108– S113,2001 .
  • 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 Transplant16 :335– 340,2001 .
  • Blake DR, Winyard PG, Marok R: The contribution of hypoxia-reperfusion injury to inflammatory synovitis: the influence of reactive oxygen intermediates on the transcriptional control of inflammation.Ann N Y Acad Sci723 :308– 317,1994 .
  • Schulz HU, Niederau C, Klonowski-Stumpe H, Halangk W, Luthen R, Lippert H: Oxidative stress in acute pancreatitis.Hepatogastroenterology46 :2736– 2750,1999 .
  • 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 Chem276 :40– 47,2001 .
  • Huang A, Vita JA, Venema RC, Keaney JF: Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin.J Biol Chem275 :17399– 17406,2000 .
  • Brown AA, Hu FB: Dietary modulation of endothelial function: implications for cardiovascular disease.Am J Clin Nutr73 :673– 686,2001 .
  • Drexler H, Hornig B: Endothelial dysfunction in human disease.J Mol Cell Cardiol31 :51– 60,1999 .
  • Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney Jr JF, Vita JA: Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease.Circulation93 :1107– 1113,1996 .
  • 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 Physiol273 :H1644– H1650,1997 .
  • Beckman JA, Goldfine AB, Gordon MB, Creager MA: Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans.Circulation103 :1618– 1623,2001 .
  • Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney Jr JF: L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease.J Clin Invest101 :1408– 1414,1998 .
  • Jackson TS, Xu A, Vita JA, Keaney Jr JF: Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations.Circ Res83 :916– 922,1998 .
  • 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 Physiol280 :H528– H534,2001 .
  • Padayatty SJ, Levine M: Vitamin C and coronary microcirculation.Circulation103 :E117 ,2001 .
  • Ness AR, Chee D, Elliott P: Vitamin C and blood pressure—an overview.J Hum Hypertens11 :343– 350,1997 .
  • 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 Hypertens16 :925– 932,1998 .
  • Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney Jr JF, Vita JA: Treatment of hypertension with ascorbic acid.Lancet354 :2048– 2049,1999 .
  • 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 Hypertens18 :411– 415,2000 .
  • Bassenge E, Fink N, Skatchkov M, Fink B: Dietary supplement with vitamin C prevents nitrate tolerance.J Clin Invest102 :67– 71,1998 .
  • Hallberg L, Brune M, Rossander-Hulthen L: Is there a physiological role of vitamin C in iron absorption?Ann N Y Acad Sci498 :324– 332,1987 .
  • Hallberg L: Wheat fiber, phytates and iron absorption.Scand J Gastroenterol Suppl129 :73– 79,1987 .
  • Hallberg L, Brune M, Rossander L: The role of vitamin C in iron absorption.Int J Vitam Nutr Res Suppl30 :103– 108,1989 .
  • Davidsson L, Walczyk T, Morris A, Hurrell RF: Influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink in Jamaican children.Am J Clin Nutr67 :873– 877,1998 .
  • 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 Nutr51 :649– 655,1990 .
  • 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 Nutr10 :351– 356,1990 .
  • 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 Surg52 :463– 466,1986 .
  • Rhode BM, Shustik C, Christou NV, MacLean LD: Iron absorption and therapy after gastric bypass.Obes Surg9 :17– 21,1999 .
  • Hunt JR, Gallagher SK, Johnson LK: Effect of ascorbic acid on apparent iron absorption by women with low iron stores.Am J Clin Nutr59 :1381– 1385,1994 .
  • Rathbone BJ, Johnson AW, Wyatt JI, Kelleher J, Heatley RV, Losowsky MS: Ascorbic acid: a factor concentrated in human gastric juice.Clin Sci76 :237– 241,1989 .
  • Sobala GM, Schorah CJ, Sanderson M, Dixon MF, Tompkins DS, Godwin P, Axon AT: Ascorbic acid in the human stomach.Gastroenterology97 :357– 363,1989 .
  • 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.Gut34 :1038– 1041,1993 .
  • 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.Carcinogenesis14 :291– 292,1993 .
  • 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.Carcinogenesis13 :2277– 2280,1992 .
  • Byers T, Guerrero N: Epidemiologic evidence for vitamin C and vitamin E in cancer prevention.American Journal of Clinical Nutrition62 :1385S– 1392S,1995 .
  • 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 Perspect108 :105– 108,2000 .
  • Schectman G: Estimating ascorbic acid requirements for cigarette smokers.Ann N Y Acad Sci686 :335– 345, discussion 345–346,1993 .
  • 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.Metabolism33 :347– 353,1984 .
  • Will JC, Byers T: Does diabetes mellitus increase the requirement for vitamin C?Nutr Rev54 :193– 202,1996 .
  • 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 Med11 :893– 898,1994 .
  • Hume R, Weyers E, Rowan T, Reid DS, Hillis WS: Leucocyte ascorbic acid levels after acute myocardial infarction.Br Heart J34 :238– 243,1972 .
  • Riemersma RA, Carruthers KF, Elton RA, Fox KA: Vitamin C and the risk of acute myocardial infarction.Am J Clin Nutr71 :1181– 1186,2000 .
  • 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 Surg86 :1296– 1301,1999 .
  • Scott P, Bruce C, Schofield D, Shiel N, Braganza JM, McCloy RF: Vitamin C status in patients with acute pancreatitis.Br J Surg80 :750– 754,1993 .
  • Dallongeville J, Marecaux N, Fruchart JC, Amouyel P: Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis.J Nutr128 :1450– 1457,1998 .
  • Padayatty SJ, Levine M: Vitamin C and myocardial infarction: the heart of the matter.Am J Clin Nutr71 :1027– 1028,2000 .
  • Enstrom JE, Kanim LE, Klein MA: Vitamin C intake and mortality among a sample of the United States population.Epidemiology3 :194– 202,1992 .
  • 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 Dieta52 :75– 91,1995 .
  • 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.Circulation92 :2142– 2150,1995 .
  • 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.JAMA282 :1233– 1239,1999 .
  • Ness AR, Powles JW: Fruit and vegetables, and cardiovascular disease: a review.Int J Epidemiol26 :1– 13,1997 .
  • 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.Neuroepidemiology16 :69– 77,1997 .
  • 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 Nutr57 :787S– 797S,1993 .
  • 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 Med134 :1106– 1114,2001 .
  • 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 Med130 :963– 970,1999 .
  • 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 Med334 :1156– 1162,1996 .
  • 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 Med130 :963– 970,1999 .
  • 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.JAMA273 :1849– 1854,1995 .
  • 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 Nutr64 :190– 106,1996 .
  • 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 Epidemiol143 :658– 664,1996 .
  • 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 Med248 :377– 386,2000 .
  • Ness AR, Powles JW, Khaw KT: Vitamin C and cardiovascular disease: a systematic review.J Cardiovasc Risk3 :513– 521,1996 .
  • 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 Cardiol13 :957– 965,1997 .
  • 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 Med123 :860– 872,1995 .
  • 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 Nutr75 :540– 549,2002 .
  • 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 Epidemiol9 :49– 80,2002 .
  • 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. 9.Arch Ophthalmol119 :1439– 1452,2001 .
  • Gale CR, Hall NF, Phillips DI, Martyn CN: Plasma antioxidant vitamins and carotenoids and age-related cataract.Ophthalmology108 :1992– 1998,2001 .
  • Block G: Epidemiologic evidence regarding vitamin C and cancer.Am J Clin Nutr54 :1310S– 1314S,1991 .
  • 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 BiomarkersPrev 10 :1201– 1205,2001 .
  • 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 Inst91 :547– 556,1999 .
  • 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 Med329 :234– 240,1993 .
  • 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 Epidemiol2 :231– 239,1992 .
  • 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 Prev9 :477– 485,2000 .
  • 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 Prev10 :17– 23,2001 .
  • 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 Med331 :141– 147,1994 .
  • 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 Nutr62 :1424S– 1426S,1995 .
  • Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K: Which plasma antioxidants are most related to fruit and vegetable consumption?Am J Epidemiol154 :1113– 1118,2001 .
  • 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, pp95– 184,2000 .
  • Pratico D: F(2)-isoprostanes: sensitive and specific non-invasive indices of lipid peroxidation in vivo.Atherosclerosis147 :1– 10,1999 .
  • 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 Med332 :1198– 1203,1995 .
  • Steinberg FM, Chait A: Antioxidant vitamin supplementation and lipid peroxidation in smokers.Am J Clin Nutr68 :319– 327,1998 .
  • 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-2′-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men.Arterioscler Thromb Vasc Biol20 :2087– 2093,2000 .
  • 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 Prev11 :7– 13,2002 .
  • Chevion M, Berenshtein E, Stadtman ER: Human studies related to protein oxidation: protein carbonyl content as a marker of damage.Free Radic Res33(Suppl) :S99– S108,2000 .
  • 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 Commun273 :729– 735,2000 .
  • 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 Oncol123 :141– 151,1997 .
  • 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 Prev9 :647– 652,2000 .
  • 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 Prev9 :1303– 1311,2000 .
  • 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 Lett132 :219– 227,1998 .
  • Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J: Vitamin C exhibits prooxidant properties.Nature392 :559 ,1998 .
  • 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 Nutr131 :1714– 1722,2001 .
  • van’t Veer PV, Kok FJ: Human studies to substantiate health effects of antioxidants. What is needed?Free Radic Res33 :S109– S115,2000 .
  • Boaz M, Green M, Fainauru M, Smetana S: Oxidative stress and cardiovascular disease in hemodialysis.Clin Nephrol55 :93– 100,2001 .
  • 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 Transplant15 :883– 887,2000 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.