Fasting-Mimicking Diet and Vitamin C a Combination Treatment for KRAS-Mutated Tumors

by | Jun 16, 2020 | 2020, Cancer, Colorectal (Colon), Vitamin C

Written by Joyce Smith, BS. This study demonstrated how a non-toxic intervention of a fasting- mimicking diet (FMD) in combination with Vitamin C can potentially affect colorectal and other KRAS- mutant cancers. 

vitamin CPrior research has shown mixed results concerning the cancer-fighting potential of vitamin C. Recent studies are showing some efficacy when used in combination with chemotherapy. High-dose vitamin C exhibits an anticancer effect through pro-oxidant reactions that produce hydrogen peroxide, with iron as a catalyst, to produce hydroxyl radicals 1-3. In turn, these free oxygen containing radicals called reactive oxygen species (ROS) cause cell DNA damage and cell death. 1-3 As a stand- alone treatment, high-dose vitamin C is ineffective against KRAS-mutated tumors 4 (tumors containing the mutated KRAS gene that regulates cell growth, maturation and death); however, when used in combination with other treatments, high-dose vitamin C’s anti-cancer potential can be enhanced.

The Di Tano research team has already shown that FMDs can reduce tumor growth and sensitize various types of cancer cells to chemotherapy 5, while at the same time protecting normal cells from chemotherapy’s damaging toxicity 5,6, two processes known respectively as “Differential Stress Sensitization” and “Differential Stress Resistance”. FMD is a plant-based, calorie-restricted, low sugar and high fat diet which is alternately cycled weekly with a normal diet to minimize lean body mass. In the present research, 7 the team investigated whether a FMD will enhance the anticancer activity of vitamin C, alone or in combination with standard chemotherapy, particularly with respect to colorectal cancer (CRC). Their findings revealed that cycling FMD enhanced the anti-cancer effect of high-dose vitamin C against KRAS-mutated tumors, both in vitro and in vivo and that adding chemotherapy further enhanced the anti-cancer effect of the FMD- vitamin C combination.

The science team cultured human and murine CRC cell lines as well as KRAS-mutant lung cancer cells and pancreatic ductal adenocarcinoma cells in control mediums and a FMD-like medium with or without vitamin C. They found that KRAS-mutated tumor cells were more susceptible to vitamin C compared to the non-mutant KRAS cells, whereas prostate, ovarian and normal colon cell lines were unaffected by vitamin C.  When treating different mouse models with a combination of FMD and vitamin C (4g/kg twice daily), Di Tong and team found that KRAS-mutated tumor progression was slowed down in the different mouse models, results that were consistent with their in vitro models. The FMD and vitamin C combination, when given weekly, was the most effective and was safe and well-tolerated.

The research team explain that Vitamin C, as a stand-alone treatment, appears to trigger the KRAS-mutant cells to protect cancer cells by increasing levels of ferritin, a protein that binds to iron; however, FMD increases vitamin C’s toxicity by reducing ferritin levels in KRAS-mutant cancer cells, consequently increasing reactive iron, oxygen species, and cell death. This effect is further enhanced by chemotherapy. An analysis of the Cancer Genome Atlas Database validates that KRAS-mutated colorectal cancer patients with low intratumor ferritin mRNA levels have a longer 3- and 5-year overall survival potential.

Di Tano and colleagues effectively demonstrated that a combination of two treatments, a fasting-mimicking diet and vitamin C, when used in combination may become a future cancer treatment with the potential to replace more toxic treatment protocols for KRAS-mutated cancers. Using FMD to sensitize cancer cells to chemotherapy through ROS production which damages their DNA is an inexpensive and feasible treatment option. Combining it with Vitamin C (also safe and inexpensive) exacerbates ROS production and when chemotherapy is added to the equation, the most synergistic effect is achieved.   The research team recommend randomized controlled clinical trials to further validate the use of FMDs and vitamin C as an intervention with low toxicity against colorectal cancer and possibly other KRAS-mutated tumors.

Source: Di Tano, Maira, Franca Raucci, Claudio Vernieri, Irene Caffa, Roberta Buono, Maura Fanti, Sebastian Brandhorst et al. “Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers.” Nature communications 11, no. 1 (2020): 1-11.

© The Author(s) 2020. Open Access This article is licensed under a Creative CommonsAttribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/. https://doi.org/10.1038/s41467-020-16243-3

Click here to read the full text study.

Posted June 16, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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