Gut microbiota modulation as a possible mediating mechanism for fasting-induced alleviation of metabolic complications: a systematic review

Background Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens. Method A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study. Results The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid–producing Lachnospiraceae. Conclusion The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.

Estrogen-related receptor alpha and Rplp1 ribosome protein-dependent translation coordinately regulate starvation response and decrease NASH progression

Although general translation declines during fasting, maintaining the translation of a subset or proteins is necessary for metabolic homeostasis and cell viability. Using unbiased proteome analysis of hepatic cells during starvation, we identified a novel pathway in which Esrra-mediated transcription of Rplp1-dependent translation of lysosomal proteins declined during early starvation and recovered after prolonged starvation to restore autophagy-lysosome function. Interestingly, hepatic Esrra-Rplp1-dependent translation rate of lysosomal proteins also was impaired in patients and mice with non-alcoholic steatohepatitis (NASH), and translational response to starvation was dysregulated in mice with NASH. Remarkably, activation of Esrra pharmacologically, genetically, or by alternate day fasting restored protein translation, increased expression of lysosomal proteins, induced autophagy, and reduced lipotoxicity, inflammation, and fibrosis in cell culture and in vivo models of NASH. Thus, hepatic Esrra is essential for ribosome-dependent translation of lysosomal proteins during starvation, and prevention of lipotoxicity and progression in NASH.

Cardiometabolic Benefits of Intermittent Fasting

This review aims to summarize the effects of intermittent fasting on markers of cardiometabolic health in humans. All forms of fasting reviewed here—alternate-day fasting (ADF), the 5:2 diet, and time-restricted eating (TRE)—produced mild to moderate weight loss (1–8% from baseline) and consistent reductions in energy intake (10–30% from baseline). These regimens may benefit cardiometabolic health by decreasing blood pressure, insulin resistance, and oxidative stress. Low-density lipoprotein cholesterol and triglyceride levels are also lowered, but findings are variable. Other health benefits, such as improved appetite regulation and favorable changes in the diversity of the gut microbiome, have also been demonstrated, but evidence for these effects is limited. Intermittent fasting is generally safe and does not result in energy level disturbances or increased disordered eating behaviors. In summary, intermittent fasting is a safe diet therapy that can produce clinically significant weight loss (>5%) and improve several markers of metabolic health in individuals with obesity.

Independent of Calorie Intake, Short-term Alternate-day Fasting Alleviates NASH, With Modulation of Markers of Lipogenesis, Autophagy, Apoptosis, and Inflammation in Rats

Non-alcoholic steatohepatitis (NASH) is a worldwide health problem. Alternate-day fasting (ADF), although thought to be aggressive, has proven safety and efficacy. We aimed to evaluate the effect of short-term ADF against already established high-fat-fructose (HFF)-induced NASH, independent of the amount of calorie intake, and to study the effect of ADF on lipogenesis, apoptosis, and hepatic inflammation. Male Sprague Dawley rats were divided into two groups: (1) negative control and (2) NASH group fed on HFF for 9 weeks, and then randomized into two subgroups of either HFF alone or with ADF protocol for 3 weeks. The ADF could improve HFF-related elevation in serum lactate dehydrogenase and could decrease the mRNA expression of lipogenesis genes; acetyl CoA carboxylase, peroxisome proliferator-activated receptor γ, and peroxisome proliferator-activated receptor α; apoptotic genes caspase-3, p53, and inflammatory cyclo-oxygenase 2; and immunohistochemical staining for their proteins in liver with upregulation of LC3 and downregulation of P62 immunoexpression. Moreover, ADF ameliorated HFF-induced steatosis, inflammation, ballooning, and fibrosis through hematoxylin and eosin, Oil Red O, and Sirius Red staining, confirmed by morphometric analysis, without significant weight loss. Significant correlation of morphometric parameters with levels of gene expression was found. These findings suggest ADF to be a safe effective therapeutic agent in the management of NASH

Reversion to regular diet with alternate day fasting can cure grade-I non-alcoholic fatty liver disease (NAFLD) in high-fructose-intake-associated metabolic syndrome

Background Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem that accompanied the obesity epidemic and is considered as the hepatic component of metabolic syndrome (MetS). Modification of lifestyle of MetS patients remains the focus to reverse and prevent progression of hepatic steatosis to NAFLD and its worsening to severe forms. The present study investigates the possible curability of metabolic syndrome -associated grade-1 NAFLD merely by alternate day fasting with or without reversion to regular diet in adult male rats. The present study was performed on 66 local strain male rats aged (6–10 m.) distributed randomly into C group (n = 12), on regular rat diet; and M group (n = 54) on high fructose- intake. On the 8th week, then rats were subjected to measurement of BW, BMI, WC, FBG, IPGTT, HDL-C, TGs, and liver histopathology, to include MetS rats randomly into four experimental groups for 4 weeks as follows: MS (n = 14); MSRD (n = 12); MSF (n = 13); and MSRDF (n = 12). On the 12th week, all rats were subjected to measurements of BW, BMI, WC, LW, LW/BW, VFW, VFW/BW, FBG, IPGTT, Ins., HOMA-IR, HbA1C, TGs, TC, LDL-C, HDL-C, CRP, Alb., bilirubin, ALT, L-MDA, and liver histopathology. Results On the 8th week, M group developed MerS and grade-I NAFLD with score-4 hepatosteatosis (69%). On the 12th week, MS group had grade-1 NAFLD with score-4 hepatosteatosis (82%) with significantly increased Ins., HOMA-IR, HDL-C, LW, LW/BW, L-MDA, ALT, CRP, and significantly decreased Alb. than C rats. Both MSRD and MSF groups had grade-1 NAFLD with score-3 hepatosteatosis (42%) with significantly decreased Ins., HOMA-IR, TC, LDL-C, LW, LW/BW, L-MDA, ALT, CRP, and significantly increased HDL-C and Alb. than MS group. MSRDF rats showed cure of grade-1 NAFLD and significantly decreased LW than other groups and normalized HOMA-IR, HbA1C TC, LDL-C, ALT, and CRP. Conclusion One month of alternate-day fasting and regular rat diet could cure grade-I NAFLD associated with Mets due to high fructose intake possibly by attenuating metabolic disorders. These two interventions might be recommended in the management of MetS patients with grade 1-NAFLD disease.

Effect of Various Types of Intermittent Fasting (IF) on Weight Loss and Improvement of Diabetic Parameters in Human

Purpose of Review A number of recent studies have suggested that intermittent fasting is as effective as traditional calorie restriction (CR) for weight loss and for cardioprotection. However, it is still unclear whether IF improves diabetes risk indicators as does CR. This review provides an overview of various patterns of intermittent fasting and shows the effect of intermittent fasting on human anthropometric such as excess body weight and biochemical parameters for example high glucose and fasting insulin, which are risk factors for diabetes. Recent Findings There is a growing body of evidence pointing to the benefits of intermittent fasting for glucose and insulin homeostasis, but this should be confirmed by further studies in population groups with (or at high risk) type II diabetes and insulin resistance. Long-term studies are also needed that could reveal potential negative health effects that some studies report. Summary Eleven studies in overweight/obese adult people that included changes in weight, body composition, and diabetic parameters (fasting glucose, fasting insulin, HbA1c concentration, and HOMA-IR index) were published between 2012 and 2020. Seven studies concerning the effects of alternate day fasting (ADF) on weight loss and diabetic parameters were analyzed. All of them have shown the effects of ADF on weight loss and slight improvement in diabetic parameters. For time-restricted feeding (TRF), a significant improvement in the HOMA-IR index was observed in 2 studies. One study saw an increase in fasting glucose. An analysis of 2 studies using a complete alternate day fasting (CADF) was performed. One study showed decrease in fasting glucose and insulin, and in one a decrease in glycosylated hemoglobin (HbA1c) was observed. Conclusion Different types of intermittent fasting reduce body weight and reduce diabetes parameters such as fasting glucose, fasting insulin, HOMA-IR index, and glycated hemoglobin (HbA1c).

EFFECT OF INTERMITTENT FASTING DIET ON TRIGLYCERIDE LEVELS IN SPRAGUE DAWLEY RATS

Triglycerides are the main lipid components that are stored in adipose tissue for energy sources. Increased triglyceride levels can lead to cardiovascular disease. One way to lower triglyceride levels is diet. The intermittent fasting diet is one of the diets that can be done, where this diet is a diet with time and calorie restrictions. The intermittent fasting diet is divided into 3 methods, namely Time restricted feeding, Alternate-day fasting and Modified fasting. This study was conducted to see the effect of an intermittent fasting diet on triglyceride levels. This research is an experimental study using white rats of Sprague Dawley strain as experimental. White rats will be divided into 3 groups of intermittent fasting diet and 1 control group and given a diet according to the group for 1 month. Weights and blood draws were performed at the beginning and end of the study, then the results of the intermittent fasting diet intervention were compared with the control group. There was a significant reduction in body weight with a p value of 0.000 and a significant decrease in triglyceride levels with a p value of 0.035 (p <0.05). Keywords : Triglycerides, Intermittent Fasting Diet, Weight loss.

Health Effects of Alternate Day Fasting Versus Pair-Fed Caloric Restriction in Diet-Induced Obese C57Bl/6J Male Mice

Alternate day fasting (ADF) induces weight loss and improves various markers of health in rodents and humans. However, it is unclear whether the benefits of ADF are derived from the lower caloric intake of ADF or from the 24-h fasting period. Therefore, this study directly compared selected markers for health – such as glucose control, body weight, liver triglycerides, T cell frequencies, and others – in high-fat (60% calories from fat) diet-induced obese mice subjected to either ADF or caloric restriction (CR). Obese mice were randomly assigned to one of four groups: (1) ADF: remained on the high-fat diet, but fed on alternate days (n = 5), (2) PF: remained on the high-fat diet, but pair-fed to the ADF group (n = 5), (3) LF: moved to a chow ad libitum diet (n = 5; 17% calories from fat), and (4) HF: remained on the high-fat ad libitum diet (n = 5). An additional group of non-obese mice maintained on a chow diet since weaning were used as controls (CON: n = 5). After 10 weeks, ADF, PF, and LF mice ate fewer kcals, had a lower body mass, had smaller epididymal fat pads, improved glucose tolerance, and had a lower hepatic triglyceride content relative to HF mice (p &lt; 0.05), but none reached that of CON mice in these measures. T cell frequencies of the spleen, blood, and mesenteric lymph nodes were reduced in ADF, PF, and HF compared to the CON group. Importantly, there were no significant differences between the ADF and PF groups in any of the measurements made in the current study. These data suggest that ADF, PF, and LF diets each lead to improved markers of health relative to high-fat diet-induced obese mice, and that the caloric restriction associated with ADF is the major factor for the noted improvements.

Health Effects of Alternate-Day Fasting in Adults: A Systematic Review and Meta-Analysis

Background: Alternate-day fasting (ADF) method is becoming more and more popular among adults. This meta-analysis aims to evaluate the effects of ADF on adults.Methods: Randomized controlled trials (RCTs) of ADF were searched using PubMed (1988 to March 2020), EMBASE (1995 to March 2020), and the Cochrane Controlled Trials Register. A systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The datum was calculated by RevMan version 5.3.0. The original references for relating articles were also reviewed.Results: Seven randomized controlled trials involving 269 participants (152 in the ADF group and 117 in the control group) were studied. In this meta-analysis, compared with the control group, the ADF group showed statistically significant reductions in weight (p &lt; 0.00001) and body mass index (p &lt; 0.00001). Besides, the ADF group showed significant differences in terms of total cholesterol (p = 0.001), low-density lipoprotein (p = 0.01), triglycerides (p = 0.02), fat mass (p = 0.002), lean mass (p = 0.002), systolic blood pressure (p = 0.003), diastolic blood pressure (p = 0.007), and total calorie intake (p = 0.007). At the same time, the analysis demonstrated that the ADF group had a same effect compared with control group in aspects of high-density lipoprotein (p = 0.27), homeostasis model assessment-insulin resistance (p = 0.55), and fasting blood sugar (p = 0.09).Conclusions: This meta-analysis suggests that ADF is a viable diet strategy for weight loss, and it has a substantial improvement in risk indicators for diseases in obese or normal people.