The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer

PLoS One. 2013 Jun 5;8(6):e65522. doi: 10.1371/journal.pone.0065522. Print 2013.

Abstract

Introduction: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.

Methods: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging.

Results: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls.

Conclusions: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Animals
  • Blood Glucose
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Diet, Ketogenic*
  • Hyperbaric Oxygenation*
  • Male
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / blood
  • Neoplasms, Experimental / secondary
  • Neoplasms, Experimental / therapy
  • Weight Loss

Substances

  • Blood Glucose
  • 3-Hydroxybutyric Acid

Grant support

This work was supported by the Office of Naval Research, ONR grant N000140610105 and ONR-DURIP equipment grant N000140210643 (http://www.onr.navy.mil/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.