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Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.
Guo, Y, Luo, S, Ye, Y, Yin, S, Fan, J, Xia, M
The Journal of clinical endocrinology and metabolism. 2021;(1):64-79
Abstract
CONTEXT Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. OBJECTIVE The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). DESIGN AND SETTING A randomized clinical trial was conducted at a community health service center. PATIENTS Participants included adults with MS, age 30 to 50 years. INTERVENTION Intervention consisted of 8 weeks of "2-day" modified IF. MAIN OUTCOME MEASURE Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. RESULTS Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. CONCLUSION IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS.
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Innate immune remodeling by short-term intensive fasting.
Qian, J, Fang, Y, Yuan, N, Gao, X, Lv, Y, Zhao, C, Zhang, S, Li, Q, Li, L, Xu, L, et al
Aging cell. 2021;(11):e13507
Abstract
Previous studies have shown that long-term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short-term intensive fasting, a complete water-only fasting has little been studied. Here, we used multi-omics tools to evaluate the impact of short-term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72-h fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions. Specifically, short-term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down-turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short-term intensive fasting. Finally, proteomic analysis of leukocytes showed that short-term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short-term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.
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3.
[Intermittent fasting : A solution for metabolic disorders?].
Collet, TH, Pataky, Z
Revue medicale suisse. 2021;(720-1):59-62
Abstract
The management of obesity comprises lifestyle changes targeting nutrient content, eating behavior and regular physical activity. Medication (orlistat, liraglutide) and bariatric surgery can later be used, but they require a clear indication and a close follow-up. Studies in chronobiology are now exploring the metabolic benefits of intermittent fasting, which restricts food intake and calorie-containing beverages to a certain window of the 24h cycle, or to certain days of the week/month, thus reinstating the alternance between anabolism and catabolism. However, the current scientific evidence is limited by the sample size and duration of the studies. It is therefore too early for a blanket strategy based on intermittent fasting in all patients with metabolic disorders.
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Effects of Intermittent Fasting or Calorie Restriction on Markers of Lipid Metabolism in Human Skeletal Muscle.
Liu, B, Hutchison, AT, Thompson, CH, Lange, K, Wittert, GA, Heilbronn, LK
The Journal of clinical endocrinology and metabolism. 2021;(3):e1389-e1399
Abstract
CONTEXT Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR). OBJECTIVE In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle. DESIGN Seventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups). RESULTS IF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels. CONCLUSIONS In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage.
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Twelve Months of Time-restricted Eating and Resistance Training Improves Inflammatory Markers and Cardiometabolic Risk Factors.
Moro, T, Tinsley, G, Pacelli, FQ, Marcolin, G, Bianco, A, Paoli, A
Medicine and science in sports and exercise. 2021;(12):2577-2585
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Abstract
INTRODUCTION Recently, a modified intermittent fasting protocol was demonstrated to be able to maintain muscle mass and strength, decrease fat mass, and improve some inflammation and cardiovascular risk factors in healthy resistance-trained males after 2 months. The present study sought to investigate the long-term effects on these parameters. METHODS The experiment was a single-blind randomized study. Twenty healthy subjects were enrolled and underwent 12 months of either a time-restricted eating (TRE) diet or a normal diet (ND) protocol, along with resistance training. In the TRE protocol, subjects consumed their energy needs in three meals during an 8-h period of time each day (1 pm, 4 pm, and 8 pm). Subjects in the ND group also had three meals, which were consumed at 8 am, 1 pm, and 8 pm. Groups were matched for kilocalories consumed and macronutrient distribution at baseline. RESULTS After 12 months of TRE, body mass, fat mass, insulin-like growth factor 1, and testosterone were significantly lower compared with ND. Moreover, inflammatory markers (interleukin 6, interleukin 1β, and tumor necrosis factor α), insulin sensitivity (fasting glucose, insulin, and homeostatic model assessment for insulin resistance index), and lipid profile (cholesterol, HDL, and LDL) significantly improved after TRE compared with ND. Finally, subjects in TRE spontaneously decreased their daily energy intake, whereas those in ND maintained their starting kilocalories per day. No adverse events were reported. CONCLUSIONS Our results suggest that long-term TRE combined with a resistance training program is feasible, safe, and effective in reducing inflammatory markers and risk factors related to cardiovascular and metabolic diseases.
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Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.
Patikorn, C, Roubal, K, Veettil, SK, Chandran, V, Pham, T, Lee, YY, Giovannucci, EL, Varady, KA, Chaiyakunapruk, N
JAMA network open. 2021;(12):e2139558
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Abstract
IMPORTANCE Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. OBJECTIVE To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. EVIDENCE REVIEW PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. FINDINGS A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. CONCLUSIONS AND RELEVANCE In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.
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Eat, Train, Sleep-Retreat? Hormonal Interactions of Intermittent Fasting, Exercise and Circadian Rhythm.
Haupt, S, Eckstein, ML, Wolf, A, Zimmer, RT, Wachsmuth, NB, Moser, O
Biomolecules. 2021;(4)
Abstract
The circadian rhythmicity of endogenous metabolic and hormonal processes is controlled by a complex system of central and peripheral pacemakers, influenced by exogenous factors like light/dark-cycles, nutrition and exercise timing. There is evidence that alterations in this system may be involved in the pathogenesis of metabolic diseases. It has been shown that disruptions to normal diurnal rhythms lead to drastic changes in circadian processes, as often seen in modern society due to excessive exposure to unnatural light sources. Out of that, research has focused on time-restricted feeding and exercise, as both seem to be able to reset disruptions in circadian pacemakers. Based on these results and personal physical goals, optimal time periods for food intake and exercise have been identified. This review shows that appropriate nutrition and exercise timing are powerful tools to support, rather than not disturb, the circadian rhythm and potentially contribute to the prevention of metabolic diseases. Nevertheless, both lifestyle interventions are unable to address the real issue: the misalignment of our biological with our social time.
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Preferential Metabolic Improvement by Intermittent Fasting in People with Elevated Baseline Red Cell Distribution Width: A Secondary Analysis of the WONDERFUL Randomized Controlled Trial.
Horne, BD, Muhlestein, JB, May, HT, Le, VT, Bair, TL, Bennett, ST, Knowlton, KU, Anderson, JL
Nutrients. 2021;(12)
Abstract
Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. The subjects enrolled were aged 21-70 years and were free of statins, anti-diabetes medications, and chronic diseases, and had ≥1 metabolic syndrome feature, as well as elevated low-density lipoprotein cholesterol. Subjects were randomized to 24-h, water-only fasting (twice per week for 4 weeks, once per week for 22 weeks) or 26 weeks of ad libitum eating. Subjects (N = 71; n = 38 intermittent fasting, n = 33 controls) had more substantial changes in insulin in intermittent fasting vs. controls (-3.45 ± 2.27 vs. 0.48 ± 3.55 mIU/L) when baseline RDW size distribution (RDW-SD) was ≥median (42.6 fL) than
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Impact of Ramadan Diurnal Intermittent Fasting on Hypoglycemic Events in Patients With Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials and Observational Studies.
Abdelrahim, D, Faris, ME, Hassanein, M, Shakir, AZ, Yusuf, AM, Almeneessier, AS, BaHammam, AS
Frontiers in endocrinology. 2021;:624423
Abstract
Ramadan is the 9th month of the lunar calendar during which Muslims abstain from food and drink between dawn and sunset for 30 consecutive days. Ramadan fasting is observed by all healthy Muslim adults, as well many Muslims with type 2 diabetes (T2DM). Hypoglycemic events (HE) are a serious complication associated with diabetes management and are associated with increased cardiovascular disease risk. Conflicting results have been reported concerning the incidence of HE among people with T2DM observing Ramadan fasting. This review summarizes available scientific evidence on the occurrence of HE and the effects of different moderators on the incidence of HE among patients with T2DM during Ramadan. We conducted a systematic review of available observational studies and randomized controlled trials (RCTs) for patients with T2DM who fasted during Ramadan, with HE as the primary outcome. Ten databases were searched for relevant studies from inception until October 31, 2020. In total, 68 studies (35 RCTs and 33 observational studies) met the inclusion criteria. Non-sulfonylureas hypoglycemic medications showed superior effects in lowering the incidence of HE over sulfonylureas hypoglycemic medications. Variable moderators were associated with experiencing HE during Ramadan in both observational studies and RCTs, including sex, geographical location, body anthropometric indicators, season, dietary behaviors, fasting duration, time since diagnosis, and pre-fasting education. This comprehensive systematic review covered the largest number of observational and clinical studies investigating the impact of Ramadan on HE among patients with T2DM. The study highlights the significance of different moderators that influence the effect of Ramadan fasting on HE, including dietary behaviors, fasting time duration, sex, season, country, pre-fasting education, age, and time since diagnosis. The study also highlighted the impact of different hypoglycemic medications on HE and noted the superiority of non-sulfonylureas over sulfonylureas hypoglycemic medications in lowering the risk for hypoglycemia in people with T2DM during Ramadan fasting.
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Does four-week consecutive, dawn-to-sunset intermittent fasting during Ramadan affect cardiometabolic risk factors in healthy adults? A systematic review, meta-analysis, and meta-regression.
Jahrami, HA, Faris, ME, I Janahi, A, I Janahi, M, Abdelrahim, DN, Madkour, MI, Sater, MS, Hassan, AB, Bahammam, AS
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(8):2273-2301
Abstract
AIMS: This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29-30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression. DATA SYNTHESIS We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18-85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = -0.092, 95% confidence interval (CI): -0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = -0.127, 95% CI: -0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = -0.115, 95% CI: -0.197, -0.034); VLDL-C (K = 13, N = 648, Hedge's g = -0.252, 95% CI: -0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = -0.255, 95% CI: -0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = -0.082, 95% CI: -0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan. CONCLUSIONS RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.