Journal Mobile Options
Table of Contents
Vol. 26, No. 2, 2003
Issue release date: 2003
Kidney Blood Press Res 2003;26:100–106

Vitamin C in Chronic Kidney Disease and Hemodialysis Patients

Deicher R. · Hörl W.H.
Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Wien, Österreich

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate represents one of the most prominent antioxidants both in plasma as well as intracellulary, exerting beneficial effects by an inhibition of lipid peroxidation and by reducing endothelial dysfunction. However, in the presence of transition metals like iron, ascorbate may give rise to an increased generation of oxidants, and ascorbylation may impose additional carbonyl stress to uremic patients. Unsupplemented dialysis patients have reportedly lower plasma levels of ascorbate in comparison to healthy controls, mostly due to a loss into the dialysate or, in case of not dialyzed patients, increased urinary losses. Currently, 60 mg of ascorbate are recommended for chronic kidney disease patients, and 1–1.5 g of oral ascorbate/week in case of suspected subclinical ascorbate deficiency or 300 mg parenteral ascorbate/dialysis session, respectively. Ascorbate’s role in modifying arterial blood pressure remains unclear, but anemic patients with functional iron deficiency might benefit from short-term, moderately dosed ascorbate supplements.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Foley RN, Parfrey, PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32(suppl 3):112–119.
  2. Hasselwander O, Young IS: Oxidative stress in chronic renal failure. Free Radic Res 1998;29:1–11.
  3. Galli F, Canestrari F, Bellomo G: Pathophysiology of the oxidative stress and its implication in uremia and dialysis. Contrib Nephrol. Basel, Karger, 1999, vol 127, pp 1–31.
  4. Parthasarathy S, Khan-Merchant N, Penumetcha M, Khan BV, Santanam N: Did the anitoxidant trials fail to validate the oxidation hypothesis? Curr Atheroscler Rep 2001;3:392–398.
  5. Frei B, England L, Ames BN: Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989;86:6377–6381.
  6. Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, Day N: Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: A prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 2001;357:657–663.
  7. Loria CM, Klag MJ, Caulfield LE, Whelton PK: Vitamin C status and mortality in US adults. Am J Clin Nutr 2000;72:139–145.
  8. Kurl S, Tuomainen TP, Laukkanen JA, Nyyssonen K, Lakka T, Sivenius J, Salonen JT: Plasma vitamin C modifies the association between hypertension and risk of stroke. Stroke 2002;33:1568–1573.
  9. Weber P, Bendich A, Schalch W: Vitamin C and health – A review of recent data relevant to human requirements. Int J Vitam Nutr Res 1996;66:19–30.
  10. Langlois M, Duprez D, Delanghe J, De Buyzere M, Clement DL: Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 2001;103:1863–1868.
  11. Lim PS, Wang NP, Lu TC, Wang TH, Hsu WM, Chan EC, Hung WR, Yang CC, Kuo IF, Wei YH: Evidence for alterations in circulating low-molecular weight antioxidants and increased lipid peroxidation in smokers on hemodialysis. Nephron 2001;88:127–133.
  12. Lonn EM, Yusuf S: Is there a role for anitoxidant vitamins in the prevention of cardiovascular diseases: An update on epidemiological and clinical trials data. Can J Cardiol 1997;13:957–965.
  13. Darko D, Dornhorst A, Kelly FJ, Ritter JM, Chowienczyk PJ: Lack of effect of oral vitamin C on blood pressure, oxidative stress and endothelial function in type II diabetes. Clin Sci 2002;103:339–344.
  14. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002;360:23–33.
  15. Buettner GR: The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol and ascorbate. Arch Biochem Biophys 1993;300:535–543.
  16. Sies H, Stahl W, Sundquist AR: Antioxidant functions of vitamins. Vitamin E and C, β-carotene, and other caretenoids. Ann NY Acad Sci 1992;669:7–20.
  17. Meister A: Mitochondrial changes associated with glutathione deficiency. Biochem Biophys Acta 1995;1271:35–42.
  18. Cárcamo JM, Bórquez-Ojeda O, Golde DW: Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways. Blood 2002;99:3205–3212.
  19. Kozlov AV, Ceccarelli D, Bini A, Meletti E, Gallesi D, Giovannini F, Masini A, Tomasi A: Low temperature EPR characterization of ‘free’ iron pools in liver in experimental iron overload: Effect of combined ethanol intoxication. J Magn Reson Anal 1997;3:141–148.
  20. Lehnen-Beyel I, De Groot H, Rauen U: Enhancement of iron toxicity in L929 cells by D-glucose: Accelerated (re-)reduction. Biochem J 2002;368:517–526.
  21. Courtois F, Delvin E, Ledoux M, Seidman E, Lavoie JC, Levy E: The antioxidant BHT normalizes some oxidative effects on iron + ascorbate on lipid metabolism in Caco-2 cells. J Nutr 2002;132:1289–1292.
  22. Adhirai M, Selvam R: Effect of cyclosporin A on tissue lipid peroxidation and membrane bound phosphatases in hyperoxaluric rat and the protection by vitamin E pretreatment. Jpn J Med Sci Biol 1997;50:9–17.
  23. Lee SH, Yoon YC, Jang YY, Song JH, Han ES, Lee CS: Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes. Pharmacol Res 2001;43:161–171.
  24. Rehman A, Collis CS, Yang M, Kelly M, Diplock AT, Halliwell B, Rice-Evans C: The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Commun 1998;246:293–298.
  25. Wolff SP, Jiang ZY, Hunt JV: Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 1991;10:339–352.
  26. Nagaraj RH, Shamsi FA, Huber B, Pischetsrieder M: Immunochemical detection of oxalate monoalkylamide, an ascorbate-derived Maillard reaction product in the human lens. FEBS Lett 1999;453:327–330.
  27. Miyata T, Wada Y, Cai Z, Iida Y, Horie K, Yasuda Y, Maeda K, Kurokawa K, van Ypersele de Strihou C: Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. Kidney Int 1997;51:1170–1181.
  28. Argirov OK, Lin B, Olesen P, Ortwerth BJ: Isolation and characterization of a new advanced glycation end-product of dehydroascorbic acid and lysine. Biochem Biophys Acta 2003;1620:235–244.
  29. Stein G, Busch M, Muller A, Wendt T, Franke C, Niwa T, Franke S: Are advanced glycation end products cardiovascular risk factors in patients with CRF? Am J Kidney Dis 2003;41(suppl 2):52–56.
  30. Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 2000;87:840–844.
  31. Aminbakhsh A, Mancini J: Chronic antioxidant use and changes in endothelial dysfunction: A review of clinical investigations. Can J Cardiol 1999;15:895–903.
  32. Williams MJ, Sutherland WH, McCormick MP, de Jong SA, McDonald JR, Walker RJ: Vitamin C improves endothelial dysfunction in renal allograft recipients. Nephrol Dial Transplant 2001;16:1251–1255.

    External Resources

  33. Feldstein A, Krier JD, Hershman Sarafov M, Lerman A, Best PJM, Wilson SH, Lerman LO: In vivo renal vascular and tubular function in experimental hypercholesterolemia. Hypertension 1999;34:859–864.
  34. Stulak JM, Lerman A, Caccitolo JA, Wilson SH, Romero JC, Schaff HV, Rodrguez Porcel M, Lerman LO: Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia. Atherosclersosis 2001;154:195–201.
  35. Stulak JM, Lerman A, Rodriguez Porcel M, Caccitolo JA, Romero JC, Schaff HV, Napoli C, Lerman LO: Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation. J Am Soc Nephrol 2001;12:1882–1891.
  36. Ellis GR, Anderson RA, Lang D, Blackman DJ, Morris RH, Morris-Thurgood J, McDowell IF, Jackson SK, Lewis MJ Frenneaux MP: Neutrophil superoxide anion-generating capacity, endothelial function and oxidative stress in chronic heart failure: Effects of short- and long-term vitamin C therapy. J Am Coll Cardiol 2000;36:1474–1482.
  37. McKechnie R, Rubenfire M, Mosca L: Antioxidant nutrient supplementation and brachial artery reactivity in patients with coronary artery disease. J Lab Clin Med 2002;139:133–139.
  38. Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P: Effects of vitamins C and E on progression of transplant-associated arteriosclerosis: A randomised trial. Lancet 2002;359:1108–1113.
  39. D’Uscio L, Milstien S, Richardson D, Smith L, Katusic Z: Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ Res 2003;92:88–95.
  40. Hultquist M, Hegbrandt J, Nilsson-Thorell C, Lindholm T, Nilsson P, Lindén T, Hultquist-Bengtsson U: Plasma concentrations of vitamin C, vitamin E and/or malondialdehyde as markers of oxygen free radical production during hemodialysis. Clin Nephrol 1997;47:37–46.
  41. Wang S, Eide TC, Sogn EM, Berg KJ, Sund RB: Plasma ascorbic acid in patients undergoing chronic haemodialysis. Eur J Pharmacol 1999;55:527–532.
  42. Nakayama H, Akiyama S, Inagaki M, Gotoh Y, Oguchi K: Dehydroascorbic acid and oxidative stress in haemodialysis patients. Nephrol Dial Transplant 2001;16:574–579.
  43. Morena M, Cristol JP, Bosc JY, Tetta C, Forret G, Leger CL, Delcourt C, Papoz L, Descomps B, Canaud B: Convective and diffuse losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients. Nephrol Dial Transplant 2002;17:422–427.
  44. Burr ML, Sweetnam PM, Hurley RJ, Powell GH: Letter: Effects of age and intake on plasma-ascorbic acid levels. Lancet 1974;ii:163–164.
  45. Pereira AM, Hamani N, Nogueira PC, Carvalhaes JT: Oral vitamin intake in children receiving long-term dialysis. J Ren Nutr 2000;10:24–29.
  46. Singh RG, Gupta AK, Dubey SS, Usha, Sharma MR: Ascorbic acid status in uremics. Indian J Med Res 1992;96:266–269.
  47. Rumsey SC, Levine M: Absorption, transport, and disposition of ascorbic acid in humans. J Nutr Biochem 1998;9:116–130.
  48. Bohm V, Tiroke K, Schneider S, Sperschneider H, Stein G, Bitsch R: Vitamin C status of patients with chronic renal failure, dialysis patients and patients after renal transplantation. In J Vitam Nutr Res 1997;67:262–266.
  49. Du Plessis AS, Randall H, Escreet E, Höll M, Conradie M, Moosa MR, Labadarios D, Herselman MG: Nutritional status of renal transplant patients. S Afr Med J 2002;92:68–74.
  50. Kalantar-Zadeh K, Kopple JD, Deepak S, Block D, Block G: Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire. J Ren Nutr 2002;12:17–31.
  51. Olmedilla B, Granado F, Southon S, Wright AJ, Blanco I, Gil-Martinez E, Berg H, Corridan B, Roussel AM, Chopra M, Thurnham DI: Serum concentrations of carotenoids and vitamins A, E and C in control subjects from five European countries. Br J Nutr 2001;85:227–238.

    External Resources

  52. Fukunaga K, Takama K, Suzuki T: High-performance liquid chromatographic determination of plasma malondialdehyde level without a solvent extraction procedure. Anal Chem 1995;230:20–23.
  53. Makoff R: Vitamin replacement therapy in renal failure patients. Miner Electrolyte Metab 1999;25:349–351.
  54. Hörl WH: Is there a role for adjuvant therapy in patients being treated with epoetin? Nephrol Dial Transplant 1999;14(suppl 2):50–60.
  55. Tarng DC, Wei YH, Huang TP, Kuo B, Yang WC: Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int 1999;55:2477–2486.
  56. Mydlík M, Derzsiová K, Zemberová E: Influence of water and sodium diuresis and furosemide on urinary excretion of vitamin B6, oxalic acid and vitamin C in chronic renal failure. Miner Electrolyte Metab 1999;25:352–356.
  57. Hirsch IB, Atchley DH, Tsai E, Labbe RF, Chait A: Ascorbic acid clearance in diabetic nephropathy. J Diabetes Complications 1998;12:259–263.
  58. Bakaev V, Efremov A, Tityaev I: Low levels of dehydroascorbic acid in uremic serum and the partial correction of dehydroascorbic acid deficiency by haemodialysis. Nephrol Dial Transplant 1999;14:1472–1474.
  59. Clermont G, Lecour S, Cabanne J, Motte G, Guilland JC, Chevet D, Rochette L: Vitamin E-coated dialyzer reduces oxidative stress in haemodialysis patients. Free Radic Biol Med 2001;31:233–241.
  60. Al-Ghamdi JM, Al-Jafari AA, Alhomida AS, Sobki SH, Al-Sulaiman MH, Al-Khader AA: Whole blood total, reduced and oxidized ascorbic acid levels in Saudi patients with chronic renal failure: influence of gender and chronic haemodialysis. Med Sci Res 1998;26:343–347.
  61. Miyata T, Ueda Y, Yamada Y, Izuhara Y, Wada T, Jadoul M, Saito A, Kurokawa K, van Ypersele de Strihou C: Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: Carbonyl stress in uremia. J Am Soc Nephrol 1998;9:2349–2356.
  62. Puskas F, Gergely P Jr, Banki K, Perl A: Stimulation of the pentose phosphate pathway and glutathione levels by dehydroascorbate, the oxidized form of vitamin C. Faseb J 2000;14:1352–1361.
  63. Qutob S, Dixon SJ, Wilson JX: Insulin stimulates vitamin C recycling and ascorbate accumulation in osteoblastic cells. Endocrinology 1998;139:51–56.
  64. Root-Bernstein R, Busik JV, Henry DN: Are diabetic neuropathy, retinopathy and nephropathy caused by hyperglycemic exclusion of dehydroascorbate uptake by glucose transporters? J Theor Biol 2002;216:345–359.
  65. Goldenberg H, Schweinzer E: Transport of vitamin C in animal and human cells. J Bioenerg Biomembr 1994;26:359–367.
  66. Will JC, Byers T: Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996;54:193–202.
  67. Vander Jagt DJ, Harrison JM, Ratliff DM, Hunsaker LA, Vander Jagt DL: Oxidative stress indices in IDDM subjects with and without long-term diabetic complications. Clin Biochem 2001;34:265–270.
  68. Craven PA, DeRubertis FR, Kagan VE, Melhem M, Studer RK: Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-β and glomerular size in diabetes. J Am Soc Nephrol 1997;8:1405–1414.
  69. Gaede P, Poulsen HE, Parving HH, Pedersen O: Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients. Diab Med 2001;18:756–760.

    External Resources

  70. Ness AR, Chee D, Elliott P: Vitamin C and blood pressure: an overview. J Hum Hypertens 1997;11:343–350.
  71. Svetkey LP, Loria CM: Blood pressure effects of vitamin C: what’s the key question? Hypertension 2002;40:789–791.
  72. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GH, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N, for the DASH-Collaborative Research Group: A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336:1117–1124.
  73. Working Party for European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure: European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;14(suppl 5):1–50.
  74. Gastaldello K, Vereerstraeten A, Nzame-Nze T, Vanherweghem JL, Tielemans C: Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by ascorbic acid administration. Nephrol Dial Transplant 1995;10(suppl 6):44–47.
  75. Tarng DC, Huang TP: A parallel, comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload. Nephrol Dial Transplant 1998;13:2867–2872.
  76. Sezer S, Ozdemir FN, Yakupoglu U, Arat Z, Turan M, Haberal M: Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients. Artif Organs 2002;26:366–370.
  77. Giancaspro V, Nuzziello M, Pallotta G, Sacchetti A, Petrarulo F: Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial. J Nephrol 2000;13:444–449.
  78. Ziai F, Habicht A, Bieglmayer C, Deicher R, Hörl WH: Erythropoetin-Bedarf in Abhängigkeit vom Vitamin-C-Status bei Hämodialysepatienten (abstract). Nieren- und Hochdruckkrankheiten 2002;31:437.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50