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Effects of short-term fasting on cancer treatment.

ABSTRACT: Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a feasible approach to enhance the efficacy and tolerability of chemotherapy. Clinical research evaluating the potential of STF is in its infancy. This review focuses on the molecular background, current knowledge and clinical trials evaluating the effects of STF in cancer treatment. Preliminary data show that STF is safe, but challenging in cancer patients receiving chemotherapy. Ongoing clinical trials need to unravel if STF can also diminish toxicity and increase efficacy of chemotherapeutic regimes in daily practice.

SUBMITTER: de Groot S

PROVIDER: S-EPMC6530042 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Effects of short-term fasting on cancer treatment.

de Groot Stefanie S Pijl Hanno H van der Hoeven Jacobus J M JJM Kroep Judith R JR

Journal of experimental & clinical cancer research : CR 20190522 1

Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a fe ...[more]

PMID: 31113478

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Project description:Background: A greater decrease in 24-hour energy expenditure (EE) during fasting and a smaller increase in 24-hour EE during low-protein overfeeding (metabolic "thrifty" phenotype) predict weight gain. As thyroid hormones (TH) are implicated in energy intake and metabolism, we assessed whether: (i) TH concentrations are altered by 24-hour fasting or overfeeding diets with varying protein content and (ii) diet-related changes in TH correlate with concomitant changes in EE. Methods: Fifty-eight euthyroid healthy subjects with normal glucose regulation underwent 24-hour dietary interventions including fasting, eucaloric feeding, and five overfeeding diets in a crossover design within a whole-room indirect calorimeter to measure the 24-hour EE. Overfeeding diets (200% of energy requirements) included three diets with 20% protein, one diet with 3% protein (low-protein overfeeding diet [LPF]: 46% fat), and one diet with 30% protein (high-protein overfeeding diet [HPF]: 44% fat, n = 51). Plasma free thyroxine (fT4), free triiodothyronine (fT3), and fibroblast growth factor 21 (FGF21) concentrations were measured after overnight fast the morning of and after each diet. Results: On average, fT4 increased by 8% (+0.10 ng/dL, 95% confidence interval [CI 0.07-0.13], p < 0.0001) and fT3 decreased by 6% (-0.17 pg/mL [CI -0.27 to -0.07], p = 0.001) after 24-hour fasting, whereas both fT4 and fT3 decreased by 5% (-0.07 ng/dL [CI -0.11 to -0.04], p < 0.0001) and 4% (-0.14 pg/mL [CI -0.24 to -0.04], p = 0.008) following HPF, respectively. Greater decreases in fT3 after HPF are associated with larger decreases in FGF21 (r = 0.40, p = 0.005). Following LPF, the mean fT3 increased by 6% (+0.14 pg/mL [CI 0.05-0.2], p = 0.003) with no change in fT4 (p = 0.7). No changes in TH were observed after normal-protein overfeeding diets (all p > 0.1). No associations were observed between TH concentrations and diet-related changes in 24-hour EE during any diet (all p > 0.07). Conclusions: Acute (200%) short-term (24 hours) changes in food intake induce small changes in TH concentrations only after diets with low (0% fasting and 3% protein overfeeding) or high (30% protein overfeeding) protein content. The fT3-FGF21 association after high-protein overfeeding suggests a role for TH in inhibiting FGF21 secretion by the liver during protein excess. These results indicate that TH are involved in protein metabolism; however, they do not mediate the short-term EE response to diets that characterize the metabolic phenotypes and determine the individual susceptibility to weight gain.

Project description:The first objective of this study was to demonstrate the usefulness of the microencapsulation technique to protect fumaric acid and thymol, avoiding their early absorption and ensuring their slow release throughout the gastrointestinal tract (GIT). For this purpose, the release of a lipid matrix microencapsulated brilliant blue (BB) was assessed in vitro, using a simulated broiler intestinal fluid, and in vivo. In vitro results showed that more than 60% of BB color reached the lower intestine, including 26.6 and 29.7% in the jejunum and ileum, respectively. The second objective was to determine the effects of microencapsulated fumaric acid, thymol, and their mixture on the performance and gut health of broilers challenged with a short-term fasting period (FP). One-day-old male ROSS 308 chickens (n = 280) were randomly distributed into seven treatments, with 10 replicates of four birds each. Dietary treatments consisted of a basal diet as negative control (NC), which was then supplemented by either non-microencapsulated fumaric acid (0.9 g/kg), thymol (0.6 g/kg), or a mixture of them. The same additive doses were also administered in a microencapsulated form (1.5 and 3 g/kg for the fumaric acid and thymol, respectively). At day 21, chickens were subjected to a 16.5-h short-term FP to induce an increase in intestinal permeability. Growth performance was assessed weekly. At day 35, ileal tissue and cecal content were collected from one bird per replicate to analyze intestinal histomorphology and microbiota, respectively. No treatment effect was observed on growth performance from day 1 to 21 (p > 0.05). Microencapsulated fumaric acid, thymol, or their mixture improved the overall FCR (feed conversion ratio) and increased ileal villi height-to-crypt depth ratio (VH:CD) (p < 0.001) on day 35 of the experiment. The microencapsulated mixture of fumaric acid and thymol increased cecal abundance of Bacteroidetes, Bacillaceae, and Rikenellaceae, while decreasing that of Pseudomonadaceae. These results indicate that the microencapsulation technique used in the current study can be useful to protect fumaric acid and thymol, avoiding early absorption, ensure their slow release throughout the GIT, and improve their effects on fasted broiler chickens.

Dataset Information

Effects of short-term fasting on cancer treatment.

Publications

Effects of short-term fasting on cancer treatment.

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