Human ancestors often resorted to fasting when stricken with an illness as a way to prevent infectious or abnormally growing cells from circulating the blood stream and inhabiting other parts of the body. Two new studies find that our ancestors may have been on to something - restricting calories in mice has shown to greatly decrease tumor volumes in subjects receiving chemotherapy.
Although the scientists are not quite sure yet how fasting leads to a better immune response to cancerous cells, the findings from their recent studies show that fasting recruits more cancer-killing, cytotoxic T lymphocytes to the scene of the cancer crime. Tumors are often guilty of producing immunosuppressive molecules that help them “hide” from the immune system, but new studies in mice suggest that the game of hide-and-seek could soon be over.
One of the studies published in the journal Cancer Cell comes from the lab of Valter Longo, Stefano Di Biase, and Changhan Lee from the University of Southern California (USC). Their method of mimicking fasting in their mouse subject was to restrict their diet to low sugar, low protein, high fat, and low-calorie foods to meet a balance of challenging the cancer cells without starving the healthy cells. After collecting data for over six weeks from mice ridden with breast or skin cancers, researchers saw both the influx of cytotoxic T lymphocytes as well as the tumors of mice receiving both chemotherapy and the restricted diet shrinking to less than half of the volume of the tumors in mice receiving only chemotherapy.
“T cells are essential for the toxicity of the fasting plus chemotherapy to cancer cells,” Longo said. He and his team discovered that the fasting and chemotherapy combination brings out cytotoxic T lymphocytes by reducing levels of an enzyme called heme oxygenase-1. Normally at high levels in tumor cells, heme oxygenase-1 has anti-inflammatory functions and has been implicated in carcinogenesis and tumor progression in previous studies.
The second Cancer Cell study was conducted by several scientists from INSERM and the Centre de Recherche des Cordeliers in France. Instead of mimicking fasting with diet restriction, the researchers used drugs called caloric restriction mimetics. They “selectively trigger” the induction of the same biochemical environment that stems from actual fasting without actually leading to any weight loss. The mimetic drug they used was called hydroxycitrate, and they tested the drug in mice with lung and breast cancers in a similar fashion to the other study.
The calorie restriction mimetics technique proved to be equally as effective as the diet restriction approach: researchers saw a reduction of both tumor size and total number of tumors.
Coming up next in the realm of fasting to fight cancer is making sure the trend the researchers saw in mice in cancer will be the same in humans. And, as always, with human trials comes the issue of safety - which Longo is already working on proving. Cancer cells gotta eat too. Let’s starve them out!
Sources: Cell Press, Journal of Biomedical Science