Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

Intermittent fasting and the liver: Focus on the Ramadan model

Intermittent fasting(IF)is an intervention that involves not only dietary modific-ations but also behavioral changes with the main core being a period of fasting alternating with a period of controlled feeding.The duration of fasting differs from one regimen to another.Ramadan fasting(RF)is a religious fasting for Muslims,it lasts for only one month every one lunar year.In this model of fasting,observers abstain from food and water for a period that extends from dawn to sunset.The period of daily fasting is variable(12-18 hours)as Ramadan rotates in all seasons of the year.Consequently,longer duration of daily fasting is observed during the summer.In fact,RF is a peculiar type of IF.It is a dry IF as no water is allowed during the fasting hours,also there are no calorie restrictions during feeding hours,and the mealtime is exclusively nighttime.These three variables of the RF model are believed to have a variable impact on different liver diseases.RF was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improve-ments in anthropometric measures,metabolic profile,and liver biochemistry regardless of the calorie restriction among lean and obese patients.The situation is rather different for patients with liver cirrhosis.RF was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of cirrhosis.Cirrhotic patients developed new ascites,ascites were increased,had higher serum bilirubin levels after Ramadan,and frequently developed hepatic encephalopathy and acute upper gastrointestinal bleeding.These complications were higher among patients with Child class B and C cirrhosis,and some fatalities occurred due to fasting.Liver transplant recipients as a special group of patients,are vulnerable to dehydration,fluctuation in blood immunosuppressive levels,likelihood of deterioration and hence observing RF without special precautions could represent a real danger for them.Patients with Gilbert syndrome can safely observe RF despite the minor elevations in serum bilirubin reported during the early days of fasting.

Advances in intermittent fasting and neurodegeneration

Intermittent fasting is a kind of diet that extends the fasting time every day or several days per week.It mainly includes time-limited eating,alternate day fasting and periodic fasting.Intermittent fasting triggers evolutionary indications and conserved cellular responses to protect and improve body status by triggering a"metabolic switch"from hepatogenic glucose to adipocyte-derived ketone bodies.Gut microbiota and circadian rhythms have also been linked to intermittent fasting.This article focuses on the research progress of intermittent fasting and neurodegenerative diseases in order to provide a theoretical basis for nutritional treatment of neurodegenerative diseases.

Effects of intermittent fasting on health markers in those with type 2 diabetes:A pilot study

AIMTo determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM).METHODSWe describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase.RESULTSAt baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m2]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P < 0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82 ± 1.18). The increased fasting duration improved at-goal (< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours).CONCLUSIONThe results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.

The role and its mechanism of intermittent fasting in tumors:friend or foe?

Intermittent fasting(IF)is becoming a prevailing topic worldwide,as it can cause changes in the body’s energy metabolism processes,improve health,and affect the progression of many diseases,particularly in the circumstance of oncology.Recent research has shown that IF can alter the energy metabolism of tumor cells,thereby inhibiting tumor growth and improving antitumor immune responses.Furthermore,IF can increase cancer sensitivity to chemotherapy and radiotherapy and reduce the side effects of these traditional anticancer treatments.IF is therefore emerging as a promising approach to clinical cancer treatment.However,the balance between long-term benefits of IF compared with the harm from insufficient caloric intake is not well understood.In this article,we review the role of IF in tumorigenesis and tumor therapy,and discuss some scientific problems that remain to be clarified,which might provide some assistance in the application of IF in clinical tumor therapy.

Potential role of intermittent fasting on decreasing cardiovascular disease in human immunodeficiency virus patients receiving antiretroviral therapy

Cardiovascular disease(CVD)has become one of the commonest causes of comorbidity and mortality among People living with human immunodeficiency virus(HIV)(PLWH)on antiretroviral therapy(ART).Nearly 50%of PLWH are likely to have an increased risk of developing CVD,including coronary heart disease,cerebrovascular disease,peripheral artery disease and aortic atherosclerosis.Aside from the common risk factors,HIV infection itself and side effects of antiretroviral therapy contribute to the pathophysiology of this entity.Potential non-pharmacological therapies are currently being tested worldwide for this purpose,including eating patterns such as Intermittent fasting(IF).IF is a widespread practice gaining high level of interest in the scientific community due to its potential benefits such as improvement in serum lipids and lipoproteins,blood pressure(BP),platelet-derived growth factor AB,systemic inflammation,and carotid artery intima-media thickness among others cardiovascular benefits.This review will focus on exploring the potential role of intermittent fasting as a non-pharmacological and cost-effective strategy in decreasing the burden of cardiovascular diseases among HIV patients on ART due to its intrinsic properties improving the main cardiovascular risk factors and modulating inflammatory pathways related to endothelial dysfunction,lipid peroxidation and aging.Intermittent fasting regimens need to be tested in clinical trials as an important,cost-effective,and revolutionary coadjutant of ART in the fight against the increased prevalence of cardiovascular disease in PLWH.

The beneficial effects of intermittent fasting:an update on mechanism,and the role of circadian rhythm and gut microbiota

Importance:There is accumulating evidence that intermittent fasting(IF)is connected to improved health condition and longevity time-restricted feeding(TRF)is the most recognized and extensively studied model of IF.Objective:To investigate the underlying mechanism of pleiotropic benefits of IF and hint the most advantageous feeding pattern for humans.Evidence review:We searched MEDLINE,EMBASE,Cochrane Library and Google Scholar by 2020 April for publications on IF or TRF and their mechanisms.Studies include animal models and human cohorts.Findings:One important mechanism is that IF allows certain period of fasting time,in which our bodies activate pathways of repair and rejuvenation.Moreover,the advantages of IF,especially TRF over total caloric restriction(CR)provided bases for various animal and human studies which suggested that the feeding-fasting rhythm stimulates the fluctuation of our gut microbiota and a series of subsequent molecular alterations,which in turn restored a healthier circadian clock that resembled our inherent clock formed throughout millions of years of homo sapiens history.Conclusions and Relevance for Reviews:Complete understanding of the mechanism leading to the beneficial effects of IF paves the way for tailored dietary regimen to combat a wide range of diseases and ill health conditions.

Current Evidence Concerning Effects of Ketogenic Diet and Intermittent Fasting in Patients with Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.

Gut microbiotad-a positive contributor in the process of intermittent fasting-mediated obesity control

Historically,intermittent fasting(IF)has been considered as an effective strategy for controlling the weight of athletes before competition.Along with excellent insight into its application in various spaces by numerous studies,increasing IF-mediated positive effects have been reported,including anti-aging,neuro protect ion,especially obesity control.Recently,the gut microbiota has been considered as an essential manipulator for host energy metabolism and its structure has been reported to be sensitive to dietary structure and habits,indicating that there is a potential and strong association between IF and gut microbiota.In this paper,we focus on the crosstalk between these symbionts and energy metabolism during IF which hold the promise to optimize host energy metabolism at various physical positions,including adipose tissue,liver and intestines,and further improve milieu internal homeostasis.Moreover,this paper also discusses the positive function of a potential recommendatory strain(Akkermansia muciniphila)based on the observational data for IF-mediated alternated pattern of gut microbiota and a hopefully regulatory pathway(circadian rhythm)for gut microbiota in IF-involved improvement on host energy metabolism.Finally,this review addresses the limitation and perspective originating from these studies,such as the association with tissue-specific bio-clock and single strain research,which may continuously reveal novel viewpoints and mechanisms to understand the energy metabolism and develop new strategies for treating obesity,diabetes,and metabolic disorders.

Effects of time-restricted eating with different eating duration on anthropometrics and cardiometabolic health:A systematic review and meta-analysis

BACKGROUND Time-restricted eating(TRE)is a dietary approach that limits eating to a set number of hours per day.Human studies on the effects of TRE intervention on cardiometabolic health have been contradictory.Heterogeneity in subjects and TRE interventions have led to inconsistency in results.Furthermore,the impact of the duration of eating/fasting in the TRE approach has yet to be fully explored.AIM To analyze the existing literature on the effects of TRE with different eating durations on anthropometrics and cardiometabolic health markers in adults with excessive weight and obesity-related metabolic diseases.METHODS We reviewed a series of prominent scientific databases,including Medline,Scopus,Web of Science,Academic Search Complete,and Cochrane Library articles to identify published clinical trials on daily TRE in adults with excessive weight and obesity-related metabolic diseases.Randomized controlled trials were assessed for methodological rigor and risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials(RoB-2).Outcomes of interest include body weight,waist circumference,fat mass,lean body mass,fasting glucose,insulin,HbA1c,homeostasis model assessment for insulin resistance(HOMA-IR),lipid profiles,C-reactive protein,blood pressure,and heart rate.RESULTS Fifteen studies were included in our systematic review.TRE significantly reduces body weight,waist circumference,fat mass,lean body mass,blood glucose,insulin,and triglyceride.However,no significant changes were observed in HbA1c,HOMA-IR,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,heart rate,systolic and diastolic blood pressure.Furthermore,subgroup analyses based on the duration of the eating window revealed significant variation in the effects of TRE intervention depending on the length of the eating window.CONCLUSION TRE is a promising chrononutrition-based dietary approach for improving anthropometric and cardiometabolic health.However,further clinical trials are needed to determine the optimal eating duration in TRE intervention for cardiovascular disease prevention.

Feasibility and metabolic effects of a 5:2 fasting intervention in women with breast cancer during radiotherapy

Purpose Obesity and insulin resistance appear to worsen prognosis of breast cancer patients.We conducted a feasibility study to test a 5:2 fasting regime in breast cancer patients undergoing radiotherapy.The intervention was rated as beneficial if it would be able to reduce fat mass while significantly improving insulin sensitivity.Methods A total of 13 non-metastatic breast cancer patients were recruited and instructed to completely abstain from food on two non-consecutive days(minimum 24 h)per week during radiotherapy.Body composition was measured weekly by bioimpedance analysis.Blood parameters were assessed before and at the end of radiotherapy.The product of triglycerides and glucose was used as a proxy for insulin sensitivity.A control group on an unspecified standard diet was assigned by propensity score matching.Results A total of twelve patients completed the study.Three patients reported side effects during fasting which were mild(grade 1).Two patients reported feeling bad while fasting,whereas five had a generally good or very good feeling.The fasting group experienced an average decrease of approximately 200 g body mass(p<0.0001),200 g(p=0.002)fat mass and 100 g muscle mass(p=0.047)per week,resulting in absolute reductions of 2.45±1.19 kg body mass,1.5±1.6 kg fat mass and 0.7±0.4 kg muscle mass.There was no improvement in insulin sensitivity and other markers of metabolic health except for gamma-glutamyltransferase which decreased by-7±8 U/l.There was also no indication that 5:2 fasting protected against acute skin toxicity.Conclusions 5:2 fasting is safe and feasible for breast cancer patients during radiotherapy and suitable to significantly reduce fat mass,but beneficial metabolic effects could not be confirmed.To improve these results,future studies could combine 5:2 fasting with carbohydrate restriction,increased protein intake and/or exercise.