Reply: Vitamin E Supplementation in Cystic Fibrosis

Abstract

To the Editor: We are grateful for the opportunity to respond to Dr. Winklhofer-Roob's detailed critique of our article, which was, as described in our introduction, a study around normal clinical practice in the setting of a children's cystic fibrosis (CF) clinic. In our study, conducted between 1989 and 1991, we were able to exploit the fact that measurement of erythrocyte α-tocopherol levels was being undertaken before the implementation throughout our clinic population of current supplementation guidelines, affording an invaluable opportunity to study steady-state α-tocopherol concentrations at various levels of supplementation, as opposed to Dr. Winklhofer-Roob's study of short-term changes in erythrocyte α-tocopherol response to a single dose of the vitamin (1). As we state, many patients were, at the beginning of the study, receiving no supplementation, or daily Ketovite, which contains 15 mg of vitamin E, hence data for this dosage. In our experience, RRR-α-tocopherol alone is used in the United Kingdom, so the racemic form of the vitamin is not an issue in this study. Recent work has shown that the free phenol and esterified forms of α-tocopherol (α-tocopherol and α-tocopherol acetate, respectively) have similar bioavailabilities (2). As Dr. Winklhofer-Roob points out, the association between erythrocyte and tissue α-tocopherol concentrations have not been measured in patients with CF. In light of this, and as the α-tocopherol is bound in the membrane with polyunsaturated fatty acids, we believe that erythrocyte levels are more representative of tissue levels than the more commonly used plasma levels. In our article, some measurements are shown in graphic form only because, for clarity, we chose to tabulate only the most common supplementation regimens. Dr. Winklhofer-Roob attempts to comment on the numbers of subjects in each group when, unfortunately, tight clustering of α-tocopherol concentrations makes counting of subjects on the graphs impossible, particularly at 100 mg/day. As shown in Table 1, there were in fact 46 measurements at this dosage, and only 8 of these were below the reference range. Likewise, the distribution of data cannot be inferred from this graph. We appreciate Dr. Winklhofer-Roob's concerns regarding statistical validity where data from the same patient are used twice; this study gathered all available data on α-tocopherol concentrations within a population of patients receiving a variety of supplements, prescribed independently of α-tocopherol level, during a 2-year period. In no case were data for the same patient entered twice less than 1 year apart. The results of our study confirm and complement those carried out by Dr. Winklhofer-Roob in indicating that relatively large α-tocopherol supplements (100 mg/day) are required by most CF patients to normalise plasma levels (at this time we do not know about tissue levels directly). There are a number of variables that may have an impact on the response of a CF patient to a particular α-tocopherol supplement, and studies on the magnitude of these responses are currently under way in our group. Given the lack of understanding of the positive role that reactive oxygen species may play in cell metabolism, caution should be exercised before prescribing very large α-tocopherol supplements to all CF patients. Until we have this information, we recommend normalisation only. S. A. Peters; F. J. Kelly Children's Unit; St. Mary's Hospital; Portsmouth, England