In the first human trial of its kind, scientists showed that a fasting-mimicking diet can work synergistically with conventional therapies in cancer patients, altering their metabolisms and reshaping their immune systems [1].
What happens when you fast?
Fasting is shaping up to be a powerful addition to clinical practice. It is not a panacea that can fend off virtually every disease, but it can exert a profound effect on the human body. By altering metabolic pathways, periodic fasting can help maintain normal weight, reduce inflammation, lower blood pressure, and beneficially alter the gut microbiome [2]. But what about cancer?
Preclinical studies in mice suggest that fasting and fasting-mimicking diets (FMD) can work synergistically with anti-cancer treatments, enhancing their activity [3]. FMD is usually defined as “low calories, low carbohydrates, low protein”. Fasting and FMD reduce glucose, insulin, and insulin-like growth factor 1 (IGF1) levels, thus inhibiting the anabolic processes (biosynthesis) that help cancer cells grow. Fasting and FMD also alleviate, to a certain extent, the damage incurred by chemotherapy.
Fasting and FMD have also been shown to alter the immune system – in particular, by boosting tumor infiltration by CD8+ T cells (the effectors of antitumor immune responses) and reducing the number of immunosuppressive regulatory T cells.
Metabolic changes
This new paper describes the first human clinical trial that investigated the safety and feasibility, as well as the metabolic and immunomodulatory effects, of FMD.
The study group consisted of 101 cancer patients receiving various oncological therapies. The patients underwent several cycles of five-day restrictive FMD followed by 16 to 23 days of refeeding, depending on each patient’s anti-cancer regimen. Cancer stages and types also varied from patient to patient, and they included breast cancer, colorectal cancer, and lung cancer.
In accordance with previous research, the FMD reduced median plasma glucose levels by 18.6%, serum insulin by 50.7%, and serum IGF1 by 30.3%. These metabolic changes were correlated neither with tumor type and stage nor anti-cancer treatment. The researchers used two control groups: 9 healthy volunteers who underwent the same FMD regimen and 13 patients with advanced breast cancer on standard chemotherapy who were not subjected to FMD. Predictably, the first group experienced metabolic changes similar to the study group, while the second group did not.
Those metabolic changes appeared with every cycle of FMD, which means that systemic metabolic adaptation to the FMD did not occur. Each cycle also reduced patients’ BMI by around 4.5%, regardless of the type of concomitant treatment. Patients who were able to endure at least three FMD cycles began to fully regain weight between the cycles, which is another sign of the tolerability of FMD in cancer patients. In general, the authors report that adverse effects from the FMD were acceptably rare.
Reshaping the immune landscape
In some of the participants, the effect of FMD on the immune system was analyzed. The researchers learned that FMD reshapes the immune system in a way that promotes its anti-tumor activity. Monocytes are blood cells that are part of the innate immune system. Various monocyte subtypes have diametrically different effects on cancer, and FMD was able to reduce the abundance of two particularly nasty pro-cancer subtypes. In addition to that, FMD increased, both systemically and on the tumor level, the amount of cancer-fighting cells, such as CD8+ T cells and natural killer cells. According to the researchers, this resulted in “an enrichment of immune signatures previously associated with good prognosis and/or better response to therapies in patients with cancer… and with the activation of several antitumor immune programs.”
The researchers note that some of these immunologic modifications appear to be long-lasting – they were still detectable at least 40 days after the end of the last cycle of FMD. They hypothesize that in some clinical contexts, such as with less advanced tumors, several FMD cycles could be enough to induce a long-term reshaping of systemic immunity such that no new cycles are needed.
Conclusion
Of course, dietary interventions alone cannot beat cancer. Still, this new study proves that fasting and fasting-mimicking diets wield serious power that can work synergistically with conventional anti-cancer therapies. Several other trials of cyclic FMD in combination with anti-cancer therapies are underway (two of them include metformin), and we will continue to bring you the news.
Literature
[1] Vernieri, C., Fuca, G., Ligorio, F., Huber, V., Vingiani, A., Iannelli, F., … & de Braud, F. (2022). Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. Cancer Discovery, 12(1), 90-107.
[2] Maifeld, A., Bartolomaeus, H., Löber, U., Avery, E. G., Steckhan, N., Markó, L., … & Forslund, S. K. (2021). Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nature communications, 12(1), 1-20.
[3] Lee, C., Raffaghello, L., Brandhorst, S., Safdie, F. M., Bianchi, G., Martin-Montalvo, A., … & Longo, V. D. (2012). Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Science translational medicine, 4(124), 124ra27-124ra27.
