Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer.

Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of ß-hydroxybutyrate (ßHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies ßHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood ßHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.

Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (ßHB), hyperbaric oxygen (HBOT), or combination therapy (LG+ßHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and ßHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

Human supragingival in vivo calculus formation in relation to saturation of saliva with respect to calcium phosphates.

The aim was to establish if there is a correlation between the rate of formation of supragingival calculus and the degree of supersaturation of saliva with respect to apatite, brushite and other calcium phosphates. The rate of calculus formation was estimated by measuring the calculus formed on lingual surfaces of the lower incisors in 15 individuals during 30 days. Submandibular saliva stimulated with citric acid and resting whole saliva, alter pH determination and ultrafiltration to remove protein was analysed for calcium, phosphate, sodium, potassium and carbonate. The degree of saturation with respect to calcium phosphates was calculated using a computer program. The rate of calculus formation among the 15 participants ranged widely, from a score of 0.5 to a high of 15. A close correlation (r = 0.91) between salivary pH and degree of supersaturation was found A weak correlation between calcium and calculus formation was also found. But neither for unstimulated nor stimulated saliva was a significant relation between supersaturation with respect to any of the calcium phosphates and the rate of calculus formation observed. Therefore, taking into consideration the background of the wide range of rates of calculus formation and of degrees of supersaturation, it was concluded that relation between them is unlikely, and the use of degree of saturation as a diagnostic tool seems unreliable.