Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis

Rainer J Klement, Colin E Champ, Christoph Otto, Ulrike Kämmerer, Rainer J Klement, Colin E Champ, Christoph Otto, Ulrike Kämmerer

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow chart of the study…
Fig 1. Flow chart of the study selection procedure.
Fig 2. Forest plot of the meta-analysis…
Fig 2. Forest plot of the meta-analysis for the mean survival time ratio.
Values less than 1 indicated a beneficial effect of the KD. The observed effects Eq (1) are the effects extracted from the individual studies, while the Bayesian effect estimates Eq (2) represent the true study effects and are influenced by all the other studies.
Fig 3. Forest plot of the meta-analysis…
Fig 3. Forest plot of the meta-analysis for the hazard ratio.
Values less than 1 indicated a beneficial effect of the KD.

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