A fasting-mimicking diet used alongside supplemental vitamin C increases the anti-cancer effect of vitamin C against different KRAS-mutant cancer models both in vitro and in mice; KRAS-mutation is common in colorectal cancer and NSCLC, for example.
More than half of colorectal cancers carry KRAS or BRAF mutations. In 2015, Yun et al (1) showed that these mutant cancers ‘handle’ vitamin C in a different way and are selectively killed by higher doses of vitamin C. This was found both in vitro and in mutant mice. These mutations also occur in other cancers such as lung cancer. At high doses, vitamin C becomes a pro-oxidant and causes the formation of hydrogen peroxide and hydroxyl radicals which in turn produce reactive oxygen species (ROS) or free radicals leading to cell death. Free iron is a key component of the cause of cell death by vitamin C (2).
It is also known that fasting or fasting-mimicking diets delay tumor progression and sensitize a wide range of tumours to chemotherapy. Much of the work has been done at the University of Southern California Longevity Institute under Professor Valter Longo.
In this study (3), researchers showed that a fasting-mimicking diet could sensitise the mutant cells to the action of vitamin C, further increasing vitamin C anti-cancer activity in KRAS-mutant cancer cells by lowering ferritin levels, consequently increasing free reactive iron oxygen species in these mutant cells and increasing levels of cell death. The researchers first conducted an analysis of The Cancer Genome Atlas Database and evidenced that KRAS-mutated colorectal cancer patients with low intratumour ferritin mRNA levels had longer 3- and 5-year overall survival. They hypothesised that fasting or a fasting-mimicking diet would help lower these levels.
The researchers under Professor Valter Longo concluded that the combination of a fasting-mimicking diet and vitamin C could be a promising low toxicity intervention against colorectal cancer and possibly other KRAS-mutated tumors and should now be investigated in human Clinical trials.
Go to: What’s a Fasting-mimicking Diet?
References
- Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer; Jihye Yun et al; Science; 11 Dec 2015. https://science.sciencemag.org/content/350/6266/1391
- O2 and H2O2 mediated destruction of Fe metabolism in NSCLC and GBM; Joshua D. Schonfeld et al; Cancer Cell, August 14 2017; https://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30301-X
- Nature Communications; May 12 2020; Synergistic effect of fasting mimicking diet and vitamin C against KRAS mutated cancers - https://www.nature.com/articles/s41467-020-16243-3