Vitamin E supplementation

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oxidation resistance of total serum lipids in the men in the ASAP study. Vitamin C was prescribed to 42·5% of the placebo group and 43·3% of the vitamin E group. In a post-hoc analysis by Cox’s proportional-hazards regression, treatment effect was adjusted for vitamin C supplementation. Additionally, an interaction term for vitamin E and vitamin C supplementation was added to the model. The addition of vitamin C to the original model of treatment effect and to the smoking-adjusted model was not significant. We detected no interaction between vitamin C supplementation and vitamin E treatment. *Mona Boaz, Shmuel Smetana, Manfred S Green Institute of Nephrology, E Wolfson Medical Center and Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University and Israel Centres for Disease Control, Tel Hashomer 1

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Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM. Vitamin E attenuates oxidative stress in induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 2000; 11: 539–49. Islam KN, O’Byrne D, Devaraj S, Palmer B, Grundy SM, Jialal I. Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy. Atherosclerosis 2000; 150: 217–24. Porkkala-Sarataho E, Salonen JT, Nyyssonen K, et al. Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo2⬘-deoxyguanoxine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. Atherioscler Thromb Vasc Biol 2000; 20: 2087–93. Zieden B, Kamanskas A, Kristenson M, et al. Increased plasma 7-betahydroxycholesterol concentrations in a population with high risk for cardiovascular disease. Arteroscler Thromb Vasc Biol 1999; 19: 967–71. Colles SM, Irwin KC, Chisolm GM. Roles of multiple oxidized LDL lipids in cellular injury: dominance of 7-betahydroperoxycholesterol. J Lipid Res 1996; 37: 2018–28.

Sir—Mona Boaz and colleagues1 relate the role of oxidative stress to excessive cardiovascular mortality in haemodialysis patients and its possible prevention by supplemental antioxidant vitamin E. A risk factor that they do not mention is the routine correction of the anaemia of end-stage renal failure with recombinant human erythropoietin. To obtain the maximum response to erythropoietin and increase the haemoglobin concentration to an acceptable level as much as 1·5–2 g per year of supplemental iron must be administered to individual patients by regular intravenous infusion. Usually, iron is safely sequestered in a redox-inactive state in the blood by the transporter protein transferrin. An

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unfortunate side-effect of intravenous iron infusion in haemodialysis patients is a sudden peak in the blood iron concentration and a consequent oversaturation of transferrin, which is associated with the appearance of unbound redox-active iron.2,3 Since oxidative modification of LDL is suspected to be a causative factor in atherogenesis, intravenous iron in haemodialysis probably exacerbates the pro-oxidative state of the blood and, therefore, the risk of cardiovascular disease. Roob and colleagues3 successfully treated 22 haemodialysis patients with a single oral dose of vitamin E (1200 IU ␣tocopherol acetate) 6 h before a haemodialysis session, during which they were also infused with intravenous iron. Plasma ␣-tocopherol concentrations rose by 68% and strikingly lowered the degree of lipid peroxidation catalysed by nontransferrin-bound redox-active iron. Furthermore, abnormally low concentrations of vitamin E in erythrocyte membranes shorten the life-time of red blood cells in the circulation of haemodialysis patients, contributing to the anaemia.4 Erythrocyte concentrations of vitamin E can be raised four-fold by oral supplementation, which also has a sparing effect on the erythropoietin dose while maintaining stable haemoglobin concentrations, attributable to the prevention of oxidative haemolysis of red blood cell membranes.4,5 Vitamin E clearly has potential as a protective adjunct to reduce the risk of atherosclerosis arising from the oxidative stress that accompanies the treatment of the anaemia of chronic renal failure. Michael J Fryer Department of Biology, John Tabor Laboratories, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK (e-mail: [email protected]) 1

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Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebocontrolled trial. Lancet 2000; 356: 1213–18. Lim P-S, Wei Y-H, Yu YL, Kho B. Enhanced oxidative stress in haamodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 1999; 14: 2680–87. Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM. Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 2000; 11: 539–49. Cristol J-P, Bosc J-Y, Badiou S, et al. Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transplant 1997; 12: 2312–17. Turi S, Nemeth I, Varga I, Matkovics B. Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transplant 1999; 14: 252–53.

Elusiveness of cysticfibrosis treatment Sir—Bruce Marshall and Theodore Liou, in their Aug 19 commentary,1 emphasised the crippling limitations of existing data on the treatment of cystic fibrosis, which has been described as being based on dogma masquerading as science.2 They were, however, compelled by the evidence for aggressive treatment. Most unexpected, however, was the unsupported conclusion that a standardised approach frequently contributes to improved outcome. Lack of standardisation, as shown by the strikingly different approaches to treatment at different centres, is a real obstacle to studies of new treatments. However, evidence that standardised treatment is better than enthusiastic close attention to detail combined with treatment tailored to individual needs and preferences has yet to be obtained. T J David Booth Hall Children’s Hospital, Manchester M9 7AA, UK (e-mail: [email protected]) 1

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Marshall BC, Liou TG. Elusiveness of ideal approach to Pseudomonas aeruginosa infection complicating cystic fibrosis. Lancet 2000; 356: 613–14. David TJ. Cystic fibrosis. Arch Dis Child 1990; 65: 152–57.

Sir—Bruce Marshall and Theodore Liou1 seem unaware of how widespread the use of the so-called Danish approach is in European clinics for treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis. The standard treatment is certainly not centred on antibiotics for acute exacerbations only. The usual practice in most clinics is immediate oral and nebulised antibiotic treatment to eradicate early P aeruginosa infection. The UK Cystic Fibrosis Trust have published detailed recommendations (agreed by the UK cystic fibrosis clinic directors) for the antibiotic treatment of respiratory infections in patients with cystic fibrosis.2 These recommendations reflect current UK practice. They include immediate combined nebulised and oral antibiotic treatment when P aeruginosa is first isolated, which delays and even prevents the onset of chronic infection.3 For many years long-term nebulised antipseudomonal antibiotics have been recommended for most patients who are chronically infected with P aeruginosa to slow the

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For personal use only. Reproduce with permission from The Lancet Publishing Group.