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High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers


Objective: High-dose vitamin C therapy might mediate beneficial clinical effects by counteracting reactive oxygen species. However, concerns are raised whether this approach might provoke diametrical (ie pro-oxidative) effects. The objective was to determine ascorbyl free radical (AFR) concentrations and potential variables of pro-oxidative damage.

Design: Crossover study; six healthy males received daily infusions of 750 or 7500 mg vitamin C for six consecutive days. Fasting concentrations of vitamin C and AFR were determined daily. On day 1, concentrations of vitamin C and AFR were measured at 0.25, 0.5, 1, 2, 4 and 8 h post infusion. Plasma concentrations of thiobarbituric acid-reactive substances (TBARS), tocopherol and urine concentrations of 8-oxoguanosine were determined on days 1 and 6.

Results: Kinetic studies on day 1 showed that concentrations of vitamin C and AFR displayed parallel dose- and time-dependent kinetics and elimination was highly efficient. Vitamin C and AFR fasting concentrations on days 2–6 were slightly above the baseline, suggesting new, stable steady states. TBARS decreased in both groups, whereas tocopherol and 8-oxoguanosine concentrations remained unchanged.

Conclusion: Kinetics of AFR largely depend on plasma vitamin C concentrations and AFR is eliminated efficiently. Our data do not support induction of pro-oxidative effects in healthy volunteers given intravenous high-dose vitamin C.

Sponsorship: Pascoe Pharmazeutische Präparate GmbH, Gießen, Germany.

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  • Bates CJ (1992): Use of homocystein to stabilise ascorbic acid, or to reduce dehydroascorbic acid, during HPLC separation of large volumes of tissue extracts. Clin. Chim. Acta. 205, 249–252.

    Article  CAS  Google Scholar 

  • Bergsten P, Amitai G, Kehrl J, Dhanwal KR, Klein HG & Levine M (1990): Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Depletion and reaccumulation. Biochem. J. 265, 2584–2587.

    CAS  Google Scholar 

  • Bergsten P, Yu R, Kehrl J & Levine M (1995): Ascorbic acid transport and distribution in human B lymphocytes. Arch. Biochem. Biophys. 317, 208–214.

    Article  CAS  Google Scholar 

  • Bianchi J & Rose RC (1986): Dehydroascorbic acid and cell membranes: possible disruptive effects. Toxicology 40, 75–82.

    Article  CAS  Google Scholar 

  • Biesalski HK, Greiff H, Brodda K, Hanfer G & Bässler KH (1986): Rapid determination of vitamin A (retinol) and vitamin E (á-tocopherol) in human serum by isocratic adsorption HPLC. Int. J. Nutr. Res. 56, 319–327.

    CAS  Google Scholar 

  • Cai L, Koropatnick J & Cherian MG (2001): Roles of vitamin C in radiation-induced DNA -damage in presence and absence of copper. Chem. Biol. Interact. 137, 75–88.

    Article  CAS  Google Scholar 

  • Ellis GR, Anderson RA, Chirkov YY, Morris-Thurgood J, Jackson SK, Lewis MJ & Frenneaux MP (2001): Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure. J. Cardiovasc. Pharmacol. 37, 564–570.

    Article  CAS  Google Scholar 

  • Galley HF, Davies MJ & Webster NR (1996): Ascorbyl radical formation in patients with sepsis: effect of ascorbate loading. Free Radic. Biol. Med. 20, 139–143.

    Article  CAS  Google Scholar 

  • Goldenberg H, Grebing C & Low H (1983): NADH-monodehydroascorbate reductase in human erythrocyte membranes. Biochem. Int. 6, 1–9.

    CAS  PubMed  Google Scholar 

  • Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena LR, Yaohui Jr W & Levine M (1997): Pharmacokinetic model of ascorbic acid in healthy volunteers during depletion and repletion. Pharmacol. Res. 14, 1133–1139.

    Article  CAS  Google Scholar 

  • Guidarelli A, De Sanctis R, Cellini B, Fiorani M, Dacha M & Cantoni O (2001): Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells. Biochem. J. 365, 509–513.

    Article  Google Scholar 

  • Heitzer T, Schlinzig T, Krohn K, Meinertz T & Munzel T (2001): Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104, 2673–2678.

    Article  CAS  Google Scholar 

  • Jentzsch AM, Bachmann H, Fürst P & Biesalski HK (1996): Improved analysis of malondialdehyd in human body fluids. Free Radic. Biol. Med. 20, 251–256.

    Article  CAS  Google Scholar 

  • Jones B & Kenward MG (1989): Design and Analysis of Cross-Over Trials. London: Chapman and Hall. pp 51–59.

    Google Scholar 

  • Lee SH, Oe T & Blair IA (2001): Vitamin C-induced decomposition of lipid hydro- peroxides to endogenous genotoxins. Science 292, 2083–2086.

    Article  CAS  Google Scholar 

  • Levine M, Conry-Cantilena C, Yaohui Wang J, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J & Cantilena LR (1996): Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA 93, 3704–3709.

    Article  CAS  Google Scholar 

  • Levine M, Wang Y, Padayatty SJ & Morrow J (2001): A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA 98, 9842–9846.

    Article  CAS  Google Scholar 

  • Loft S, Vistisen K, Ewertz M, Tjonneland A, Overvad K & Poulsen HE (1992): Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender, and body mass index. Carcinogenesis. 13, 2241–2247.

    Article  CAS  Google Scholar 

  • May JM, Qu Z, Morrow JD & Cobb CE (2000): Ascorbate-dependent protection of human erythrocytes against oxidant stress generated by extracellular diazobenzene sulfonate. Biochem. Pharmacol. 60, 47–53.

    Article  CAS  Google Scholar 

  • May JM, Qu Z & Cobb CE (2001): Recycling of the ascorbate free radical by human erythrocyte membranes. Free Radic. Biol. Med. 31, 117–124.

    Article  CAS  Google Scholar 

  • Pence LA & Mennear JH (1979): Inhibition effect of dehydroascorbic acid on insulin secretion from mouse pancreatic islets. Toxicol. Appl. Pharmacol. 50, 57–65.

    Article  CAS  Google Scholar 

  • Podmore ID, Griffith HR, Karl HE, Mistry N, Mistry P & Lunec J (1998): Vitamin C exhibits pro-oxidant properties. Nature 392, 559–560.

    Article  CAS  Google Scholar 

  • Priem H, Loft S, Nyyssönen K, Salonen JT & Poulsen H (1997): No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2′-deoxyguanosin excretion in smokers. Am. J. Clin. Nutr. 65, 503–507.

    Article  Google Scholar 

  • Rose RC, Choi JL & Bode AM (1992): Short term effects of oxidized ascorbic acid on bovine corneal endothelium and human placenta. Life Sci. 50, 1543–1549.

    Article  CAS  Google Scholar 

  • Schneider M, Diemer K, Engelhart K, Zankel H, Trommer WE & Biesalski HK (2001): Protective effects of vitamin C and E on the number of micronuclei in lymphocytes in smokers and their role in ascorbate free radical formation in plasma. Free Radic. Res. 34, 209–219.

    Article  CAS  Google Scholar 

  • Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H & Shimazaki S (2000): Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch. Surg. 135, 326–331.

    Article  CAS  Google Scholar 

  • Van Duijn MM, Karmi T, Van Steveninck J, Van den Broek PAJ & Van der Zee J (2000): Erythrocytes reduce extracellular ascorbate free radicals using intracellular ascorbate as an electron Donor. J. Biol. Chem. 275, 27720–27725.

    CAS  Google Scholar 

  • Villalba JM, Canalejo A, Rodriguez-Aguilera JC, Buron MI, Morre DJ & Navas P (1993): NADH-ascorbate free radical and -ferricyanide reductase activities represent different levels of plasma membrane electron transport. J. Bioenerg. Biomembr. 25, 411–417.

    Article  CAS  Google Scholar 

  • Washko PW, Rotrosen D & Levine M (1989): Ascorbic acid transport and accumulation in human neutrophils. J. Biol. Chem. 264, 18996–19002.

    CAS  PubMed  Google Scholar 

  • Welch RW, Bergsten P, Butler JD & Levine M (1993): Ascorbic acid accumulation and transport in human fibroblasts. Biochem. J. 294, 505–510, 1993.

    Article  CAS  Google Scholar 

  • Wenzel HR, Pfleiderer G, Trommer WE, Paschenda K & Redhardt A (1976): The sythesis of spin-label derivatives of NAD+ and its structural components and their binding to lactate dehydrogenase. Biochem. Biophys. Acta. 452, 292–301.

    CAS  PubMed  Google Scholar 

  • Williams MJ, Sutherland WH, McCormick MP, de Jong SA, McDonald JR & Walker RJ (2001): Vitamin C improves endothelial dysfunction in renal allograft recipients. Nephrol. Dial. Transplant. 16, 1251–1255.

    Article  CAS  Google Scholar 

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This study was supported by Pascoe Pharmazeutische Präparate GmbH, Gießen, Germany. Data were presented at Nutrition Week 2002 in San Diego, CA and published in abstract form in Am. J. Clin. Nutr. 75: 2(S) A228 abstr (2002).

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Guarantor: HK Biesalski.

Contributors: Andreas Mühlhöfer: conception, conduct of the clinical experiment, interpretation of data, writing; Silke Mrosek: conduct and organization of the clinical experiment, measurement of variables such as vitamin C, TBARS, vitamin E, interpretation of data; this work is part of her diploma thesis; Beate Schlegel: conduct and organization of the clinical experiment, interpretation of data, writing; Wolfgang Trommer, Fabio Rozario: measurement of AFR; Hansjosef Böhles: measurement of 8-oxoguanosin; Dieter Schremmer: statistical analysis; Wolfram G. Zoller: conduct and organization of the clinical experiment, interpretation of data; Hans K. Biesalski: conception, design of the clinical experiment, interpretation of data, writing; funding by Pharmaforschungs GmbH, Gieβen.

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Correspondence to HK Biesalski.

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Mühlhöfer, A., Mrosek, S., Schlegel, B. et al. High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers. Eur J Clin Nutr 58, 1151–1158 (2004).

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