1 3 LETTER TO THE EDITOR © Springer-Verlag Berlin Heidelberg 2014 Response to commentary by Champ and Klement Is a ketogenic diet the solution for the hyperglycemia problem in glioblastoma therapy? Arnulf Mayer · Peter Vaupel · Hans-Garlich Struss · Alf Giese · Marcus Stockinger · Heinz Schmidberger Strahlenther Onkol DOI 10.1007/s00066-014-0793-z a measureable beneft from a ketogenic diet in any human cancer. Since Drs. Champ and Klement are thus not able to cite such a study, they instead refer to the case report by Zuccoli et al. [6], who speculated that the regression of a glioblastoma following incomplete resection and adjuvant chemoradiotherapy with temozolomide “could result in part from the action of the calorie-restricted ketogenic diet.” When the tumor recurred approximately 8 months later, Zuccoli et al. [6] suggested a connection with the fact that the 600 kcal/day diet prescribed was “not strictly followed” anymore at this time (see Fig. 6 in Zuccoli et al. [6]). It is conceivable that medical laymen could agree with such a conclusion due to a lack of experience with the management of this disease, but as a responsible physician and radiation oncologist Dr. Champ should clearly have cautioned against it instead of citing the study in a way that can all too easily be misinterpreted as scientifc fact. Secondly, Drs. Champ and Klement state that our “fear that ketone bodies might fuel GBM growth is not supported by any data.” It is not fear, however, but rather a physio- logical fact that forces us to consider this possibility. Brain tissue is the paradigm of an organ that is able to adapt its metabolism to utilizing ketones in the fasting state, so we do not agree that it can be safely assumed that malignant tis- sue derived from it will be consistently lacking this capabil- ity. A single immunohistochemical study that shows some reduced staining for selected enzymes of ketone metabolism is certainly not suffcient to convince us of the contrary, par- ticularly when this staining shows considerable biologically implausible nuclear components, as is the case in the study cited by Drs. Champ and Klement (reference 9 in their let- ter). Furthermore, GBMs typically do contain extensive hypoxic tissue areas that lead to locally increased glycolytic metabolism, but evidence for a generally dysfunctional oxi- dative phosphorylation (as suggested by Drs. Champ and We thank Drs. Champ and Klement for their interesting and partly provocative comments, and Strahlentherapie und Onkologie for the opportunity to respond to them. Like a considerable number of physicians, biologists, nonmedical practitioners (“Heilpraktiker”), and patients, they enthusias- tically advocate a ketogenic diet as a supportive and possibly even therapeutic measure for cancer patients, in particular for patients with glioblastoma multiforme (GBM). In the last sentence of their letter they even conclude that “the bur- den of proofng any clinically harmful effects” of ketogenic diets “rests upon those who warn against their usage.” This is a bold statement, and we have to ask the question as to whether the arguments in favor of ketogenic diets live up to the criteria of scientifc, evidence-based medicine. Firstly, Drs. Champ and Klement claim that ketogenic diets have shown “great potential for the treatment of GBM.” However, scrutiny of the literature reveals that this is not true. To date, not a single clinical study has shown Original article: Champ CE, Klement RJ (2014) Commentary on “Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme”. Strahlenther Onkol doi:10.1007/s00066-014-0788-9 A. Mayer () · P. Vaupel · M. Stockinger · H. Schmidberger Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131 Mainz, Germany e-mail: arnmayer@uni-mainz.de H.-G. Struss Department of Laboratory Medicine, University Medical Center, Mainz, Germany A. Giese Department of Neurosurgery, University Medical Center, Mainz, Germany