by Patrick Arnold ~ www.patrickarnoldblog.com
Researchers at the University of South Florida recently had some very exciting research published in the International Journal of Cancer. http://www.ncbi.nlm.nih.gov/pubmed/24615175 The research team was led by Dr. Dominic D’agostino, and the goal of the study was to examine the impact of supplemental ketones and ketone precursors on metastatic cancer in mice. The research has important implications on the treatment of cancer and also possibly on the prevention of cancer.
Ketogenic Diet, Caloric Restiction, and Cancer
Recent research has strongly suggested that the ketogenic diet may prevent the spread of metastatic cancer (metastatic cancer is cancer that can spread from the original tumor site to other parts of the body). This research was pioneered by Dr. Thomas Seyfried from Boston College. Dr. Seyfried has used the ketogenic diet in conjunction with caloric restriction to successfully restrict metastasis, and in some cases actually shrink the size of tumors.
The concept is relatively simple. Cancer cells can generally only use glucose to energize their growth, while normal cells have the metabolic flexibility to use fatty acids and ketones in addition to glucose. So by starving tumors of glucose via calorie and/or carbohydrate restriction – while simultaneously providing abundant alternative fuels for the body and brain (the ketogenic diet) – you may halt the cancer without side effects.
The concept may be quite bold, but it is not new. A Nobel Prize physicist named Otto Warburg first conceived of the general idea back in the 1920s. Unfortunately, after the discovery of the structure and function of DNA in 1953, the popular view of cancer was that it was a disease of purely genetic origin. As a consequence, Warburg’s hypotheses were largely discarded. Hopes were high that a cure for cancer was just around the corner back then, but as we all know that was not to be. Luckily, within the last few decades some researchers have taken a second look at Warburg’s work and the “metabolic theory of cancer”.*
Using this “metabolic theory of cancer” as an inspiration, studies were undertaken examining the efficacy of caloric restriction and/or ketogenic diet in cancer survival. It was found that often the growth and spread of tumors was halted, and in some case actually reversed. These findings have garnered attention and have sparked some controversy. There are concerns with the practical applications of these dietary interventions in the patient population. One concern involves the idea of initiating caloric restriction while the threat of cachexia looms. Cachexia is the condition of lean tissue wasting that often occurs as a consequence of cancer, and it is cachexia which often kills the patient rather than the tumors themselves. Could caloric restriction exacerbate cachexia in some instances and lead to an earlier demise? In addition to the cachexia issue, how readily will patients be willing to endure the restrictive and often unappetizing aspects of the ketogenic diet?
What Dr. D’agostino and his team set out to find is whether or not metastatic cancer could be controlled via exogenous supplementation alone. He designed an experiment in which three groups of mice were inoculated with a highly metatstatic line of cancer cells that contained a luminescent tag (to enable clear imaging of the tumors). All the mice were given unrestricted access to a standard diet (60% carbohydrates). One group would have the diet alone while the other two groups would receive one of two different forms of exogenous ketone compounds in addition to the diet. The two exogenous ketone supplements used were 1,3-butanediol (BD) and RS-butanediol diacetoacetate (ketone ester or KE). Their metabolic conversions to ketone bodies is exemplified in the following diagram.
The results of this experiment were remarkable. Despite being on a high carb unrestricted diet the groups taking the exogenous ketones exhibited dramatically less tumor infiltration throughout the body compared to the diet alone mice (as seen by bioluminescent imaging). Survival in the BD supplemented and KE groups were prolonged 51% and 69% respectively compared to controls as well.
These results seem to contradict much of what was assumed regarding how the ketogenic diet fights cancer. It has traditionally been thought glucose deprivation was necessary to starve the cancer. However in this study the mice were eating unrestricted amounts of a high carb diet, so glucose remained high. What could be going on here? The researchers speculate that the ketones themselves may be directly toxic to the tumor cells, via mechanisms such as disruption of energy production by glycolysis in the tumors.
This paper certainly will cause an upheaval amongst those studying dietary interventions for cancer. Now the possibility has been opened up for simple supplementation as a course of treatment using the synthetic ketone precursors used in the study, or perhaps even by using natural ketone supplements such as beta-hydroxybutyrate (BHB) salts. Supplementation would be a much simpler, convenient, and patient compliant alternative to the more drastic dietary interventions previously thought necessary.
*The metabolic theory of cancer postulates that cancer does not arise because of damage to our DNA resulting in mutated oncogenes, but rather it arises as a result to disruptions in processes of energy production in our mitochondria. The disruption of oxidative phosphorylation in the mitochondria forces a cell to rely on the less efficient glucose driven anaerobic glycolysis. It is this dysfunction in energy production which then is thought to turn on existing oncogenes in the nucleus, causing the cell to turn cancerous.
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 due to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively utilize 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 ?-hydroxybutyrate (?HB). 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 ?-hydroxybutyrate (?HB) and acetoacetate (AcAC). Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood ?HB, 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 anti-cancer 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. © 2014 Wiley Periodicals, Inc.
Copyright © 2014 UICC.