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Anti-tumor effects of ketogenic diets in mice: A meta-analysis

Klement, RJ and Champ, CE and Otto, C and Kämmerer, U (2016) Anti-tumor effects of ketogenic diets in mice: A meta-analysis. PLoS ONE, 11 (5).

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Abstract

Background: Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods: We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). Conclusions: There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Klement, RJ
Champ, CE
Otto, C
Kämmerer, U
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorCanoll, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 May 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0155050
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Radiation Oncology
Refereed: Yes
Date Deposited: 31 Aug 2016 18:06
Last Modified: 22 Jun 2021 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/28258

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