The development of glycolytic inhibition-based ketonic diet or medical foods developed for cancer pa

Since 'dysfunctional metabolic process' or 'increased glucose uptake' by cancer cell was first suggested by German biochemist Otto Warburg, ketogenic diet was proposed as an anti-cancer treatment (1). Ketogenic diet is proved to change various metabolites in blood because in this diet, glucose intake is restricted and carbohydrate intake is replaced with high fat diet (2). Therefore, applying this diet in cancer patient can limit cancer growth and later can lead to cancer death caused by the glucose limitation -main energy source of cancer-. Although it can induce cancer death, there will no bad effects in normal cell such as heart, muscle and brain cells because they are able to metabolize ketone bodies.

While cancer is one of the leading cause of mortality in Korea, the development of ketogenic diet or medical foods for cancer patients is still far. In our project, we are trying to find out whether ketogenic diet or medical food which was developed by our collaborative hospital is efficient to trigger ketosis in cancer patient after their pancreatic cancer surgery. In addition, our main objective is to reveal the development of this diet can decrease cancer recurrence and help their recovery.

In this research we are using metabolomics, a systematic study of metabolites and chemical processes they are related to. Some previous studies compared plasma metabolites of pancreatic cancer patient and noncancerous controls using GC/TOF-MS, LC/ESI-MS, LC/LTQ-Orbitrap and they proved that metabolic biomarkers such as arachidonic acid, erythritol, cholesterol, N-methylalanine were increased, while glutamine, hydrocinnamic acid, phenylalanine, tryptamine were decreased (3). For instance, some markers such as serum CA 19-9 -the only biomarker approved by US Food and Drug Administration (FDA) for the diagnosis of pancreatic cancer- will be checked in a case-controled manner (4-5). In order to show the correlation between ketosis and the change of metabolite related to pancreatic cancer, we will also confirm the change of ketosis induced metabolites (6).

The whole research project is funded by IPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.

Reference

1.Warburg, O. (1925). The metabolism of carcinoma cells. The Journal of Cancer Research, 9(1), 148-163.

2.Allen, B. G., Bhatia, S. K., Anderson, C. M., Eichenberger-Gilmore, J. M., Sibenaller, Z. A., Mapuskar, K. A., ... & Fath, M. A. (2014). Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox biology, 2, 963-970.

3.Urayama, S., Zou, W., Brooks, K., & Tolstikov, V. (2010). Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Communications in Mass Spectrometry, 24(5), 613-620.

4.Ritts, R. E., & Pitt, H. A. (1998). CA 19-9 in pancreatic cancer. Surgical oncology clinics of North America, 7(1), 93-101.

5.Goonetilleke, K. S., & Siriwardena, A. K. (2007). Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. European Journal of Surgical Oncology (EJSO), 33(3), 266-270.

6.Soeters, M. R., Serlie, M. J., Sauerwein, H. P., Duran, M., Ruiter, J. P., Kulik, W., ... & Houten, S. M. (2012). Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite. Metabolism, 61(7), 966-973.