The old saying goes, “feed a cold, starve a fever”—now scientists might add, “starve a tumor.” In mice, a low-protein, low-calorie diet sensitizes breast cancer and melanoma cells to attack by the immune system, while prodding the immune system itself to make more cancer-killing cells, according to a study in the July 11 Cancer Cell. For people, a similar diet might offer a low-cost version of the immunotherapy that has recently been successful in cancer studies, suggests study author Valter Longo, a biogerontologist at the University of Southern California in Los Angeles. Antibodies that activate the immune system, or therapies that multiply immune cell populations, are promising but also expensive and require a lengthy approval process, Longo says.
His group has found that short-term fasting makes chemotherapy more effective, but water-only fasts are hard on mice as well as patients. Therefore, the researchers designed what they call a fasting-mimicking diet, low in protein and sugar. For mice, that means a jelly-like foodstuff offering about 10 percent of the calories in their normal rations; for people, victuals high in nuts and vegetables totaling 725 calories per day.
The researchers grafted cancer cells into mice, then gave them the low-calorie diet, for four days, every two weeks. The diet alone cut the rate of tumor growth nearly in half; adding a chemotherapy drug such as doxorubicin checked cancer expansion even further. At the same time, mice on the fasting-mimicking diet had more T cells circulating in the tumors; diet and doxorubicin combined led to triple the number of T cells.
Normally, cancer cells have strategies to hide from T cells, for example by creating an unwelcoming, low-oxygen, acidic environment and decorating themselves with proteins that turn away T cells. The diet seems to drop those shields, Longo says. In so doing, it teaches the immune system to go after the cancer. The authors showed this by grafting two sets of cancer cells on either side of the mice. One graft had been starved, in cell culture, before implantation; the other not. The mice’s immune cells learned to recognize the cancer and attacked both grafts.
Human trials with the fasting-mimicking diet are already underway, Longo says, though it will be several years before he can determine if the diet affects survival rates. He suspects that the diet, adopted during the days surrounding chemo treatments, could help defeat a variety of cancers—though he wouldn’t yet recommend that cancer patients try a low-calorie diet. Jonathan Powell, an oncologist at Johns Hopkins University School of Medicine in Baltimore who was not involved in the study, worries the results such as these might prompt patients to try dangerous starvation diets. “We don’t know the exact implications for patients right now,” he says, “But certainly this provides a potential new avenue to enhance immunotherapy for cancer.”
Nonetheless, Longo estimates thousands of patients worldwide are trying a minimal diet, and some have seen significant benefits. While many oncologists aren’t ready to promote the diet, they’ll often allow it, he says.