Short-term fasting reduces tumour growth among cancer patients: study

Short-term, cyclic fasting boosts the immune system and could enhance the effectiveness of antitumour therapies. Cancer patients who underwent a short-term fasting-mimicking diet (FMD) in a safety and efficacy trial had an increase of immune cells known to participate in recognizing and killing cancer cells, said Dr. Claudio Vernieri, a medical oncologist at the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. The study, in Cancer Discovery, investigated the safety, feasibility, metabolic and immunomodulatory effects of a severely calorie restricted, five-day FMD regimen in cancer patients. It also included an interim analysis in which FMD-induced systemic and intratumor immune responses were investigated in 22 breast cancer patients enrolled in the DigesT trial. Read: Older breast cancer patients not getting as much care as younger patients The concept of severe calorie restriction in cancer is compelling because animal model studies show FMDs have additive or synergistic antitumour activity, especially when used in combination with standard anticancer therapies such as chemotherapy or immunotherapy. The anticancer effects are attributed to reductions of blood glucose, insulin and insulin-like growth factor-1 concentrations which in turn leads to an inhibition of tumour growth and proliferation. A total of 101 patients with various tumour types and undergoing standard anticancer therapies were enrolled. The FMD regimen consisted of a five-day long, low-carbohydrate, low-protein, plant-based diet. Participants were allowed to consume up to 600 kilocalories on day one and up to 300 kilocalories on days two, three, four and five for a total amount of up to 1,800 kilocalories over five days. This dietary cycle was repeated every three or four weeks for up to a maximum of eight consecutive cycles. Between the calorie-restricted periods, participants went back to their normal dietary habits for 16 to 23 days. “During the five-day FMD, patients could eat specific types of vegetables, such as green salad, cauliflowers, broccoli, onions, nuts, some fruits and zero-calorie beverages such as sugar-free tea or sugar-free coffee, in the amounts specified in the FMD scheme,” said Dr. Vernieri. Vitamin supplements were not given unless specific nutritional deficiencies were diagnosed. In those cases, targeted supplementation of vitamins or minerals were recommended by the patient’s treating physicians. Patients continued on whichever standard-of-care antitumour therapies they were on before entering the study. Blood samples were collected just before the start of each FMD cycle and at the end of each five-day FMD. Almost all the patients, 99%, completed at least one FMD cycle, 76.2% at least three FMD cycles, and 19.8% patients completed all eight FMD cycles. The reasons some patients discontinued FMD included an inability to maintain a body mass index (BMI) above 20 kg/m2 (4%); poor acceptability of the FMD (10.9%); tumour progression (21.8%); adverse events (6.9%); completed their treatment program (17.8%), or surgery. FMD-related adverse events that occurred in a small number of patients were fatigue, hypoglycemia, syncope, nausea, dizziness and increased AST levels. In 99 patients evaluated, the FMD reduced median plasma glucose concentration by 18.6%, serum insulin by 50.7% and serum IGF-1 by 30.3%. The diet increased average urinary ketones from 0.18 mg/dl to 59.9 mg/dl. The study authors noted that FMD-induced metabolic changes were independent of the type of primary tumour, concomitant anticancer treatment and tumour stage. When the blood samples were analyzed, it was found that the diet led to a downregulation of peripheral blood immunosuppressive myeloid cells, and also either boosted or activated cancer-killing cells. Calory restrictions lead to an increase of tumour-fighting immune cells “We observed that after five days of a severely calorie-restricted regimen, there was an increase of several populations of immune cells, including activated lymphocytes and natural killer cells, at both peripheral blood and intratumour levels. Of note, these immune cell populations have been previously shown to participate in recognizing and killing cancer cells, as well as in establishing long-term immunological antitumour memory,” Dr. Vernieri said. The effects persisted. Researchers found that some of the immunomodulatory effects resulting from the calorie-restrictive diet were still present a month after the completion of a single five-day FMD cycle. “At the tumour level, the desirable immunological modifications induced by FMD were observed seven to ten days after the end of the diet. Together, our results indicate that some FMD-induced immunological changes are durable, and are not rapidly reversed upon initiation of refeeding with a normal diet,” he said. More trials are needed to better understand whether FMD -induced immunological effects can potentiate the antitumour activity of immunotherapy agents used for specific tumour types, and just how much calorie restriction is needed for an effect. Several FMD regimens are being evaluated in clinical trials. “These regimens differ in terms of daily calorie content, FMD duration and specific types of foods and beverages. While these FMD approaches have a significant reduction of total calorie content and relative content in carbohydrates and proteins in common, it is not clear how strong calorie restriction should be and last to produce desirable metabolic and immunological effects,” Dr. Vernieri said. His team also launched the BREAKFAST trial to further investigate the FMD dietary approach in cancer. The idea of quasi-fasting for cancer is fairly new, according to Amy Kirkham, PhD, an assistant professor of Kinesiology and Physical Education at the University of Toronto. She was not involved in the study but is launching the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study. Details are in BMC Cancer. “Calorie restriction holds promise to provide a number of potential benefits to cancer patients. However, there is very limited research available in humans currently. We need larger randomized controlled trials to better understand the best protocol, the feasibility and the safety for cancer patients,” she said. With DREAM, researchers intend to study whether a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment can affect tumour growth. Caloric restriction and low carbohydrate intake can inhibit glycolysis (anaerobic glucose metabolism) which is used by tumours for energy. The exercise may help enhance blood flow to tumours and reduce hypoxia creating a less cancer-friendly environment.

Short-term fasting reduces tumour growth among cancer patients: study

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