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The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study.
Bauersfeld, SP, Kessler, CS, Wischnewsky, M, Jaensch, A, Steckhan, N, Stange, R, Kunz, B, Brückner, B, Sehouli, J, Michalsen, A
BMC cancer. 2018;18(1):476
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Short-term fasting (STF) has been shown to protect healthy cells against the adverse effects of chemotherapy while making tumor cells more vulnerable to it. The present randomised pilot cross-over study was designed to assess the effect of a 60 hour STF on quality of life (QOL), well-being and fatigue in patients with gynaecological cancer undergoing chemotherapy. Group A was randomised to a STF during the first three of six scheduled chemotherapies (36 h before to 24 h after the chemotherapy) followed by non-calorie restricted nutrition during the following three chemotherapies. During the fasting period subjects received unrestricted amounts of water, herbal tea, 2x100cl vegetable juice and small standardized quantities of light vegetable broth with a maximum total daily energy intake of 350 kcal. Group B was allocated to a vice versa sequence of nutrition. All measurements were performed at baseline and eight days after each chemotherapy cycle. A variety of questionnaires were used for assessment of QOL, general well-being and fatigue. 34 patients with breast or ovarian cancer completed the study. Fasting was safe and all reported side effects were of low grade. STF led to a better tolerance to chemotherapy with less compromised QOL and reduced fatigue within the 8 days after chemotherapy. At the final consultation the majority of patients reported better tolerance to chemotherapy with STF. The authors conclude that STF during chemotherapy is feasible and has beneficial effects on QOL, well-being and fatigue.
Abstract
BACKGROUND This pilot trial aimed to study the feasibility and effects on quality of life (QOL) and well-being of short-term fasting (STF) during chemotherapy in patients with gynecological cancer. METHODS In an individually-randomized cross-over trial patients with gynecological cancer, 4 to 6 planned chemotherapy cycles were included. Thirty-four patients were randomized to STF in the first half of chemotherapies followed by normocaloric diet (group A;n = 18) or vice versa (group B;n = 16). Fasting started 36 h before and ended 24 h after chemotherapy (60 h-fasting period). QOL was assessed by the FACIT-measurement system. RESULTS The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference (MID; FACT-G = 5) with STF but greater than the MID for non-fasted periods. The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects. CONCLUSION STF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy. Larger studies should prove the effect of STF as an adjunct to chemotherapy. TRIAL REGISTRATION This trial was registered at clinicaltrials.gov: NCT01954836 .
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Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.
Sutton, EF, Beyl, R, Early, KS, Cefalu, WT, Ravussin, E, Peterson, CM
Cell metabolism. 2018;27(6):1212-1221.e3
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Studies have shown that intermittent fasting (IF) can reduce body weight or body fat, as well as a number of metabolic markers. However, it is unknown whether the metabolic benefits are solely due to the weight loss. In addition, data from circadian studies suggest that eating earlier in the day has a positive effect on metabolism. The aim of this randomised, cross-over, controlled feeding trial was to evaluate the effects of early time-restricted feeding (eTRF) on weight and metabolic markers. eTRF was implemented as consuming all calories within a 6 hours window with the last meal no later than 3pm. 8 overweight men with prediabetes were randomized to either eTRF or a control schedule (12-hr feeding period) for 5 weeks, and later crossed over to the other schedule. During both eating regimes the same meals and calories were consumed in both groups in a controlled environment. eTRF improved insulin metabolism, blood pressure and oxidative stress, but not glucose levels, cholesterol or inflammatory markers. No weight loss occurred either during eTRF or control period, suggesting that the observed changes are independent of weight loss. The authors conclude that eTRF improves some aspects of cardiometabolic health and that these effects are not solely due to weight loss.
Abstract
Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.
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Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.
Cignarella, F, Cantoni, C, Ghezzi, L, Salter, A, Dorsett, Y, Chen, L, Phillips, D, Weinstock, GM, Fontana, L, Cross, AH, et al
Cell metabolism. 2018;27(6):1222-1235.e6
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Calorie restriction (CR) has potent anti-inflammatory effects and has shown beneficial effects in an animal model for Multiple Sclerosis (MS). Intermittent Fasting (IF) has similar effects as CR and may be more acceptable long term than CR. This paper reports results from both an animal study and a pilot randomised controlled human clinical trial on IF and MS. The animal study showed that IF had beneficial effects on the MS animal model and that these effects were at least in part mediated by changes in the gut microbiome. 16 patients with relapsing remitting MS were enrolled during a relapse and randomised to either IF (6-7 fasting days during the two-week study) or normal eating. Changes in immune inflammatory parameters and gut flora were seen in the IF group which were similar to the beneficial changes in the animal model. The authors conclude that larger clinical studies to test IF and microbiome manipulation as a potential treatment in MS are warranted.
Abstract
Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.
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A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics.
Han, K, Nguyen, A, Traba, J, Yao, X, Kaler, M, Huffstutler, RD, Levine, SJ, Sack, MN
Journal of immunology (Baltimore, Md. : 1950). 2018;201(5):1382-1388
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Previous studies have shown that caloric restriction and fasting may modulate immune function and have positive effects in asthmatics. The aim of this pilot study was to evaluate the effects of fasting on specific inflammatory markers that might mediate such benefits. 18 mild asthmatics, 5 of whom were not on steroid inhalers, fasted for 24 hours. Lung function and immune parameters were evaluated at baseline and 2.5 hours after the first meal following the fast. There were significant differences between subjects who were and were not on steroid inhalers. Whilst one day of fasting did not affect lung function, a number of inflammatory parameters were improved by fasting in those not taking steroid inhalers, but not in those who were taking steroids. The authors conclude that caloric restriction might be considered as a strategy to improve systemic and pulmonary inflammation in asthma.
Abstract
A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4+ T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
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Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects.
Traba, J, Kwarteng-Siaw, M, Okoli, TC, Li, J, Huffstutler, RD, Bray, A, Waclawiw, MA, Han, K, Pelletier, M, Sauve, AA, et al
The Journal of clinical investigation. 2015;125(12):4592-600
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Intermittent fasting and caloric restriction have been shown to have beneficial effects on a particular inflammatory pathway, called NLRP3 inflammasome, which is associated with insulin resistance and asthma. In this highly technical paper the authors report a study which was conducted to confirm whether the beneficial effect of fasting on the NLRP3 inflammatory pathway is mediated via a particular protein called sirtuin and its effects on mitochondria (the energy producing parts of every cell). 19 healthy subjects fasted for 24 hours followed by a set meal. Bloods were drawn after the fast and 1 hour and 3 hours after the meal and evaluated for a number of inflammatory parameters. The NLRP3 inflammasome was less active in the fasted than in the fed state. The investigators established the involvement of sirtuin and mitochondria, as well as other inflammatory pathways in this fasting induced immune modulation.
Abstract
BACKGROUND Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity. METHODS We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation. RESULTS In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting. CONCLUSIONS Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease. TRIAL REGISTRATION ClinicalTrials.gov NCT02122575 and NCT00442195. FUNDING Division of Intramural Research, NHLBI of the NIH.