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Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes

Abstract

Preclinical data provide evidence for synergism between ketogenic diets (KDs) and other oncological therapies. The aim of this systematic review was to summarize data from clinical studies that have tested KDs along with other treatments used within medical oncology. The PubMed database was searched using the key words "ketogenic" AND ("cancer" OR "glioblastoma"). A secondary search was conducted by screening the reference lists of relevant articles on this topic. Relevant studies for this review were defined as studies in which KDs were used complementary to surgery, radio-, chemo-, or targeted therapy and at least one of the following four outcomes were reported: (i) Overall survival (OS); (ii) progression-free survival (PFS); (iii) local control rate; (iv) body composition changes. Twelve papers reporting on 13 clinical studies were identified. Nine studies were prospective and six had a control group, but only two were randomized. KD prescription varied widely between studies and was described only rudimentarily in most papers. Adverse events attributed to the diet were rare and only minor (grade 1–2) except for one possibly diet-related grade 4 event. Studies reporting body composition changes found beneficial effects of KDs in both overweight and frail patient populations. Beneficial effects of KDs on OS and/or PFS were found in four studies including one randomized controlled trial. Studies in high-grade glioma patients were not sufficiently powered to prove efficacy. Evidence for beneficial effects of KDs during cancer therapy is accumulating, but more high-quality studies are needed to assess the overall strength of evidence.

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Notes

  1. 1.

    The general problems with evidence hierarchies have been thoroughly discussed. For examples see Stegenga [22] or Klement and Bandyopadhyay [23].

  2. 2.

    These two types of skepticism parallel those identified by the astronomer–philosopher Milan Ćirković regarding SETI, the search for extra-terrestrial intelligence in the Universe:”instrumentalist” (or methodological) and “fundamentalist” skepticism [29]. Indeed we argue that certain parallels can be drawn between SETI, where dogmatic principles, religious or otherwise dictate an individual’s attitude towards the endeavor, and nutrition research which is often confounded with pseudo-scientific beliefs, conflicts of interest, and dogmatism [30].

  3. 3.

    This statement is not strictly exact since the first clinical study applying a KD in cancer patients was published in 1941 and received a lot of newspaper attention. See Klement [53] for a historical review.

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Acknowledgements

We thank Dr. Adeleh Khodabakhshi for providing us individual patient data from her study that allowed us to produce Figs. 2 and 3.

Funding

No funding was received for this work.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by RJK and NB. The first draft of the manuscript was written by RJK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rainer J. Klement.

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Rainer J. Klement, Nanina Brehm, and Reinhart A. Sweeney declare that they have no conflict of interest.

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This review was undertaken without requesting ethical approval, since ethical approval was granted for most of the included studies. All human data were anonymous, and the ethical recommendations of the Declaration of Helsinki were adhered to.

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Klement, R.J., Brehm, N. & Sweeney, R.A. Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes. Med Oncol 37, 14 (2020). https://doi.org/10.1007/s12032-020-1337-2

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Keywords

  • Cancer
  • Evidence
  • High-grade glioma
  • Ketone bodies
  • Metabolic therapy
  • Skepticism