Faculty Editor: Professor Jeffrey DaCosta
ons in blood sugar and insulin levels, increased level of beneficial HDL cholesterol, and decreased level of detrimental LDL cholesterol. In addition, there have been numerous studies that show that this diet is associated with the mitigation of different diseases and disorders such as Parkinson’s, diabetes, and multiple sclerosis. How this diet works is by reducing carbohydrate intake and ingesting mainly fats so that the body goes into a state of ketosis. The body then does not have enough carbohydrates to burn, and thus begins to use fat storage as a source of energy. During this process, the liver produces ketones that supply energy for the brain.
Few studies have already been conducted with the goal of determining if a ketogenic diet could also be the key to slowing tumor progression and cancer cachexia, which is a complex metabolic disorder that results in a loss of weight and skeletal muscle in association with cancer. Cachexia, not only does it cause tremendous weight loss, but it also diminishes the quality of life in cancer patients. Cachexia is a clinical issue, which results in patients refusing treatment for cancer such as chemotherapy or radiation, but even so these types of treatment have a negative effect on nutritional status. As a result, the research team from Meiji Co. in Tokyo, Japan (Nakamura et al. 2018) came to the understanding that whatever course of treatment is decided for cancer, it should simultaneously maintain nutritional status while diminishing the size of tumors.
The research team tested the effect of a ketogenic formula (KF) diet on mice injected with colon tumor cells. In the experiment, 25 mice were randomized into three different groups: 5 normal controls, 10 tumor-bearing controls, and an experimental group of 10 tumor-bearing KF mice. The normal and tumor-bearing mice received a standard diet, and the KF mice received a ketogenic diet. Colon 26 cells (a type of cancer cells) were introduced subcutaneously into the tumor-bearing controls and KF mice. After 21 days they measured change in body weight, change in tumor weight, plasma IL-6, PGE2, and plasma βHB concentration to analyze whether their method worked. After 21 days, the values for weight and weight change was significantly lower in the tumor-bearing (TB) group than in the KF group. This also takes into account that during the experimental period that the KF group’s total energy intake was higher than TB and normal control (NR). The tumor weight was significantly lower in the KF group after 21 days than the TB group and change in carcass weight was higher in KF group than the TB group. Moreover, plasma IL-6 concentrations were significantly lower in the KF group than the TB group. Plasma βHB concentrations were three-fold higher in the KF group than in the other two groups, and there was a significant negative correlation between plasma βHB concentration and tumor weight in the TB and KF groups.
Based on these results, it appeared that the use of KF suppressed the progression of murine colon 26 tumors even in the absence of caloric restriction. KF also significantly suppressed systemic inflammatory response and muscle loss associated with cancer cachexia. It also suggests that tumor size might be correlated with blood βHB concentration, which means that a mechanism for the anti-tumor effect might be the increase of βHB concentration from the diet. The elevation of plasma IL-6 concentration was inhibited in the KF group, which also suggests that βHB elevation by KF ingestion might have suppressed the systemic inflammatory response and as a result also inhibits cancer progression. The author also suggests that another reason for tumor reduction could be the restriction of glucose. Glucose restriction increases ketone body production in the liver, which also serves as a catalyst for elevated blood βHB concentration. Different metabolic pathways (glycolytic pathways) are used by tumor cells compared to normal healthy cells, and this depends on obtaining energy from oxidative phosphorylation. As a result, restriction of glucose can also serve to reduce tumor growth.
Whether these results can be extrapolated to humans cannot be finalized yet since this is the first experiment to successfully demonstrate the anti-tumor effect of a keto diet on colon 26 cells without caloric restriction. In fact, other studies have had trouble replicating these results. For example, a research group from the University of Texas at Austin reported that a low-carb diet had no anti-tumor effect, but another research group at Boston College found that caloric restriction is necessary to show anti-tumor effects of a ketogenic diet. Nonetheless, there is evidence that a managed ketogenic formula diet can inhibit further tumor progression and prevent cancer cachexia, which is proven through improvement in muscle/body weight and inflammation prevention. Potential future questions not addressed in this study include the duration of the anti-inflammatory effect, long-term effects on survival, and interference with chemo or radiotherapy. This study hopes to pave the way for future studies in exploring the effect of ketogenic diet on colorectal cancer and for cancer beyond the gastrointestinal tract.
- Plasma IL-6 is an interleukin which regulates immune responses e.g. inflammation; acts as both pro-inflammatory and anti-inflammatory.
- Blood β-hydroxybutyrate (βHB) levels are used to evaluate the production of ketone bodies; investigates the correlation between ketone bodies and anti-tumor efficacy.
- Mawer, R. (2018, July 30). The Ketogenic Diet: A Detailed Beginner’s Guide to Keto. Retrieved from https://www.healthline.com/nutrition/ketogenic-diet-101.
- Nakamura, K., Tonouchi, H., Sasayama, A., & Ashida, K. (2018, February 14). A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852782/.