Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients - a controlled cross-over pilot study

Abstract

Background This pilot trial aimed to investigate whether modified short-term fasting (mSTF) reduces the incidence of chemotherapy-induced toxicities and whether an initial ketogenic diet (KD) as fasting supportive diet reduces fasting-related discomfort and improves the compliance. Methods In this controlled cross-over trial, gynaecologic cancer patients undergoing chemotherapy with a minimum of 4 cycles fasted for 96 h during half of their chemotherapy cycles and consumed a normocaloric diet during the other chemotherapy cycles. The caloric intake during mSTF was restricted to 25% of each patient’s daily requirement. In addition, half of the patients should eat a 6-day normocaloric KD prior to each mSTF period to investigate a KD’s hunger-suppression effect. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed at each chemotherapy. Results Thirty patients aged 30–74 years (median 54 years) completed the study. During mSTF the frequency and severity score of stomatitis [− 0.16 ± 0.06; 95% CI -0.28 - (− 0.03); P = 0.013], headaches [− 1.80 ± 0.55; 95% CI -2.89 – (− 0.71); P = 0.002], weakness [− 1.99 ± 0.87; 95% CI -3.72 – (− 0.26); P = 0.024] and the total toxicities’ score were significantly reduced [− 10.36 ± 4.44; 95% CI -19.22 - (− 1.50); P = 0.023]. We also observed significantly fewer chemotherapy postponements post-mSTF, reflecting improved tolerance of chemotherapy [− 0.80 ± 0.37; 95% CI -1.53 – (− 0.06); P = 0.034]. A significant reduction in mean body weight by − 0.79 ± 1.47 kg during mSTF was not compensated and remained until study’s conclusion (P < 0.005). On average, Insulin [− 169.4 ± 44.1; 95% CI -257.1 – (− 81.8); P < 0.001] and Insulin-like growth factor 1 levels [− 33.3 ± 5.4; 95% CI -44.1 – (− 22.5); P < 0.001] dropped significantly during fasting. The KD as a fasting supportive diet neither reduced fasting-related discomfort nor improved compliance of our fasting regimen. Conclusion MSTF is safe and feasible in gynaecologic cancer patients. Our results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and enhance the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients. Trial registration germanctr.de: DRKS00011610, registered 30 January, 2017.

Feasibility, Process, and Effects of Short-Term Calorie Reduction in Cancer Patients Receiving Chemotherapy: An Integrative Review

“…All studies concluded that SCR was safe, well-tolerated, and feasible [31][32][33][34][35][36][37]. More importantly, many participants expressed a strong motivation to undertake SCR and a desire to continue the practice in the future because of the perceived benefits of SCR, which included an increased sense of control [31][32][33].…”

“…Five studies focused on gynecologic cancer populations [31][32][33][34][35] and the other two involved various types of cancer. In the five studies that stipulated strict timelines for SCR, the total period ranged between 24-96 hours, with SCR typically starting 24-72 hours before the chemotherapy and lasting for about 24 hours after the completion of chemotherapy [31,32,[34][35][36]. The other two studies observed participants' self-determined reduction practices, and thus presented large variations in the SCR timeframe ─ the patients started SCR 24-140 hours prior to chemotherapy and ended it 5-56 hours following chemotherapy [33,37].…”

“…However, the adherence decreased to below 50% when the researchers followed for more than three cycles [34,35]. Excluding non-SCR related symptoms (such as, recurrent febrile neutropenia) and personal factors (such as, forgetting, changing chemotherapy plan, and others), the reasons for withdrawal included headache, hyperventilation, weakness, failure to regain weight, aversion to fasting nutrition, and social constraints [31,32,[34][35][36][37]. The qualitative study also reported social constraints as barriers to SCR ─ the patients who performed self-initiated SCR indicated that the protocol interfered with meal sharing in their social lives.…”

“…All researchers concluded that the possible side effects of SCR were mild, and that they either did not interfere with daily activities or did not require special treatment. The following side effects were noted: hunger, fatigue, dizziness, headache, hypoglycemia, weight loss, hyponatremia, orthostatic reaction or hypotension, and nausea after taking broth or juice [31,[35][36][37]. Although weight loss may be an expected side effect of SCR, the studies showed that the loss of body weight was absent or minimal (about 6-7 pounds, <5%) [31,35,37], and that it was regained quickly after resuming a normal diet [31,37].…”

“…The following side effects were noted: hunger, fatigue, dizziness, headache, hypoglycemia, weight loss, hyponatremia, orthostatic reaction or hypotension, and nausea after taking broth or juice [31,[35][36][37]. Although weight loss may be an expected side effect of SCR, the studies showed that the loss of body weight was absent or minimal (about 6-7 pounds, <5%) [31,35,37], and that it was regained quickly after resuming a normal diet [31,37]. While pilot studies reported that no obvious changes in parameters related to nutrition and metabolism, such as prealbumin, insulin, and glucose, were observed [32,36], larger RCTs indicated that glucose and insulin were significantly lower in SCR groups before and during the treatment than controls [34,35].…”