Preventative abilities of a ketogenic diet and intermittent fasting in relationship to the carcinogenesis of astrocytoma – Dr Ben Loos
Dr Ben Loos
Department of Physiological Sciences, Stellenbosch University
The preventative abilities of a ketogenic diet and intermittent fasting in relationship to the carcinogenesis of astrocytoma.
Carcinogenesis and the progression to cancer cells is a result of multiple genetic defects that result from exposure to dietary and environmental agents. It has been estimated that lifestyle and nutrition contribute up to 80% as determinants of cancers such as prostate or breast cancer (Go et al., 2001) The relationship between diet and carcinogenesis is now fully appreciated and many studies are under way to reduce the risk of carcinogenesis through defined dietary and life style intervention. Cancer remains the leading cause of death among the most productive age group, with astrocytomas being diagnosed predominantly between 35 and 45 of age. Astrocytomas are a malignancy with particular poor prognosis, due to the often aggressive and infiltrative growth pattern observed. Astrocytomas respond poorly to chemotherapy and radiation, and due to its network-like proliferation, it is rarely accessible to surgery.
The recent advances in our understanding of cancer metabolism indicates that protein degradation through autophagy is crucial to maintain the high metabolic demand of cancer (White et al., 2011). It has been shown that modulation of autophagic activity has a robust effect on cancer proliferation, due its potential of inducing metabolic failure. In addition, the role of autophagy in reducing and limiting genome damage, has recently been revealed (White and DiPaloa, 2009). These are crucial parameters that influence carcinogenic properties. Many selected clinical trials are currently being performed that utilize the modulation of autophagy in order to improve treatment regimen, with promising results. It is known that dietary intervention, such as a ketogenic diet (McDaniel et al., 2011), as well as short term nutrient deprivation (Hartman, 2012) both upregulate autophagic flux in the brain. This intervention has historically been reverted to due to its powerful anticonvulsant and antipeileptogenic properties. However, it remains largely unknown whether a combination of such intervention also reduces carcinogenesis in brain tumors. A number markers have recently been established that can be utilized to assess carcinogenic properties of astrocytomas. The primary aim of this study entitled:
“The preventative abilities of a ketogenic diet and intermittent fasting in relationship to the carcinogenesis of astrocytoma”
is to dissect the relationship between dietary intervention through a change in generic substrate provision (from glucose to ketone bodies) as a background diet, concomitantly with an intermittent induction of neuronal protein clearance brought about by short term nutrient deprivation and their overall effect on carcinogenesis. We ask whether this intervention is able to significantly reduce markers of carcinogenesis in astrocytomas. This study is therefore an investigation into the dietary relationship to astrocytoma carcinogenesis, with the potential to be developed into a preventative life style intervention. A unique in vitro and ex vivo approach will be utilized to address the research question most optimally, in combination with powerful analytical techniques that assess and quantify carcinogenetic properties and autophagy in conditions outlined below in great detail.
This project is unique in its idea and is derived from the growing “expertise” in our laboratory, with regards to the role of autophagy and its effect on cell death susceptibility (Loos and Engelbrecht, 2009, 2011, 20013). The project team is highly qualified with experience and expertise in respective fields. The environment for the conduction of the research is very well equipped with all the required state of the art equipment (some of them extremely unique – see chapter 19) hence the chances of a successful study implementation are very high. The project leader and principal applicant (myself) is highly motivated and has a track record of successful research implementation of this nature, student supervision and publication output. This project will significantly contribute to the knowledge base of life style, neuro-carcinogenesis and prevention of astrocytoma, and at the same time will substantially contribute to human capital development, skills training and transformation.