“Fasting-mimicking” Diet Found Safe and Potentially Helpful to Cancer Patients
Study: Short-term, severe calorie restriction can reduce sugar and other substances in blood that may feed cancer cells and boost the antitumor immune response.
A diet involving short-term, severe calorie restriction was safe and resulted in biological effects in the body that may be helpful in cancer treatment, according to the report of a clinical trial published in Cancer Discovery, a journal of the American Association for Cancer Research.
“Our results from a first-in-human clinical trial showed that a scheme of severe short-term calorie restriction was safe and biologically active in patients, and that its activity likely involved the activation of immune responses,” said Claudio Vernieri, MD, PhD, a medical oncologist at the National Cancer Institute in Milan, Italy (INT from its Italian initials). “Since calorie restriction is a safe, inexpensive, and potentially effective approach that could be easily combined with standard antineoplastic therapies, we think these findings might have relevant implications for cancer therapy.”
Preclinical research has demonstrated that severe calorie restriction in the form of cyclic fasting or fasting-mimicking diet (FMD) has potent anticancer effects when combined with standard pharmacological treatments. However, the safety and biological effects of calorie restriction in cancer patients has been poorly investigated so far.
Vernieri and colleagues enrolled 101 patients in the study with various types of cancer who were being treated with different standard anticancer therapies. The objective of the study was to assess the safety, feasibility, and metabolic effects of the FMD in cancer patients.
The researchers administered an FMD regimen that consisted of a five-day, low-carbohydrate, low-protein, plant-derived diet, which provided up to 600 Kcal on day 1 and up to 300 Kcal on days 2, 3, 4, and 5, for a total amount of up to 1,800 Kcal in five days. The cycle was repeated every three or four weeks for up to a maximum of eight consecutive cycles.
Study results demonstrated that the FMD regimen was safe, feasible, and well tolerated by the majority of patients. The incidence of severe FMD-related adverse events was 12.9 percent, the most common being fatigue, which was rarely severe.
Biological impacts included a decrease of blood glucose, insulin, and growth factor, a reduction in peripheral blood immunosuppressive cells, and enhanced intratumor T-cell infiltration in cancer patients receiving standard-of-care therapy, the study found.
”The metabolic modifications observed in our patients recapitulate those induced by calorie restriction in preclinical models, in which they are associated with potent antitumor effects,” Vernieri said.
Calorie restriction was followed by a refeeding period of 16 to 23 days, during which patients were not subjected to specific dietary restrictions but were recommended to adhere to international guidelines for a healthy diet and lifestyle.
The loss of body weight that occurred during the five days of severe calorie restriction was reversible in most of the patients during the refeeding period.
“This is an especially important finding, because it excludes the risk that patients might undergo progressive weight loss and/or malnourishment, which are associated with reduced efficacy of anticancer therapies and reduced survival,” commented co Filippo de Braud, MD, director of oncology and hematology at INT and professor of medical oncology at the University of Milan.
The investigators also evaluated the effects of the FMD on patient immune responses. In an analysis conducted on 38 patients at the end of a five-day FMD cycle, the researchers found a significant decrease of circulating immunosuppressive cells and an increase of activated T cells. Both of these effects occurred independently of concomitant antitumor therapies and were also observed in a small group of healthy volunteers.
To assess the changes at the tumor level, Vernieri and colleagues analyzed the interim results of another ongoing trial (DigesT) testing a five-day FMD cycle before surgery in early-stage breast cancer and melanoma patients. This analysis showed a significant increase in tumor-infiltrating T cells and other changes, suggesting a desirable switch toward an antitumor immune microenvironment following FMD.
“Severe calorie restriction generated a metabolic ‘shock’ that activated several populations of immune cells that could boost the antitumor activity of standard antineoplastic treatments,” said coauthor Licia Rivoltini, MD, head of the Immunotherapy of Human Tumors Unit at INT.