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Combination ketogenic diet, ketone supplementation, and hyperbaric oxygen therapy inhibits metastatic spread, slows tumor growth, and increases survival time in mice with metastatic cancer (123.7)
Author(s) -
Poff Angela,
Ward Nathan,
Seyfried Thomas,
D'Agostino Dominic
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.123.7
Subject(s) - warburg effect , ketogenic diet , cancer , ketone bodies , medicine , metastasis , tumor hypoxia , in vivo , cancer cell , cancer research , hypoxia (environmental) , adipose tissue , glycolysis , endocrinology , pharmacology , biology , chemistry , metabolism , radiation therapy , oxygen , microbiology and biotechnology , organic chemistry , psychiatry , epilepsy
Cancers express an energy metabolism characterized by fermentation in the presence of oxygen (Warburg Effect). Mitochondrial dysfunction forces most cancers to require excess glucose for energy and prevents effective ketone metabolism. Abnormal vasculature creates hypoxia which promotes growth and metastasis by activating HIF‐1, further stimulating glycolysis and enhancing the Warburg Effect. The ketogenic diet (KD) is a high fat, low carbohydrate diet that lowers glucose and elevates ketones and slows cancer progression in vivo . Ketones possess inherent anti‐cancer properties, inhibiting cancer cell proliferation and viability in vitro and prolonging survival in vivo . Hyperbaric oxygen therapy (HBOT) increases oxygenation of the tumor, reversing the cancer promoting effects of hypoxia. We have previously shown that KD + HBOT and ketone supplementation slows cancer progression as stand‐alone therapies. We hypothesized that combining these therapies would be a more effective treatment regimen. We tested this combination therapy in the VM‐M3 mouse model of metastatic cancer. Treated mice exhibited decreased tumor growth and metastatic spread to the lungs, kidneys, spleen, adipose, and liver (p<0.05). Treated mice lived 103% longer than controls (p<001). This study suggests that this combination therapy should be further investigated for potential clinical use. Grant Funding Source : Supported by Office of Naval Research and a charitable donation from Scivation Inc.