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Intermittent fasting regimens for metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis of randomized controlled trials.
Abuelazm, MT, Mohamed, I, Naeem, A, Khlidj, Y, Tanashat, M, Katamesh, BE, Abusuilik, H, Altobaishat, O, Abdelnabi, M, Abdelazeem, B
European journal of gastroenterology & hepatology. 2024;(4):371-381
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed , EMBASE , WOS , SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, -0.32; 95% CI, -0.55 to -0.09; P < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, -39.83; 95% CI, -64.78 to -14.87; P < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction ( P < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.
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Effects of an Intermittent Fasting 5:2 Plus Program on Body Weight in Chinese Adults with Overweight or Obesity: A Pilot Study.
Kang, J, Shi, X, Fu, J, Li, H, Ma, E, Chen, W
Nutrients. 2022;(22)
Abstract
To retrospectively review the efficacy of intermittent fasting 5:2 plus program (30% of energy requirements on fast days and 70% of energy requirements on nonfasting days) in Chinese patients with overweight or obesity. This retrospective cohort study evaluated weight loss outcomes of patients treated with 12 weeks weight loss program in clinic. Adults with overweight or obesity participated in intermittent fasting 5:2 plus, daily calorie restriction (70% of energy requirements every day) or daily calorie restriction with meal replacement (70% of energy requirements every day, partly provided with high-protein meal replacement) programs for 12 weeks. The primary objective was to compare the weight loss of three groups. The primary outcome measure was the change in the % total weight loss. A total of 131 patients (35.3 ± 10.1 years; 81.7% female) were included, and the mean weight loss was 7.8 ± 4.4% after 12 weeks. The intermittent fasting 5:2 plus group (n = 42) achieved 9.0 ± 5.3% weight loss, compared with 5.7 ± 3.7% in the daily calorie restriction group (n = 41) (p < 0.001) and 8.6 ± 3.5% in the meal replacement group (n = 48) (p = 0.650). A total of 85.7% of patients in the intermittent fasting 5:2 plus group lost more than 5% body weight, vs. 58.5% in the daily calorie restriction group (p = 0.008), and 45.2% lost more than 10% body weight, vs. 14.6% in the daily calorie restriction group (p = 0.005). No serious adverse events were reported in the three groups. The intermittent fasting 5:2 plus program more effectively led to weight loss than daily calorie restriction in the short-term in Chinese patients with overweight or obesity. A longer-term prospective randomized controlled trial is needed.
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Eight weeks of intermittent fasting versus calorie restriction does not alter eating behaviors, mood, sleep quality, quality of life and cognitive performance in women with overweight.
Teong, XT, Hutchison, AT, Liu, B, Wittert, GA, Lange, K, Banks, S, Heilbronn, LK
Nutrition research (New York, N.Y.). 2021;:32-39
Abstract
Human trials that compare intermittent fasting (IF) to calorie restriction (CR) with psychological, behavioral and cognition outcomes are limited. We hypothesized that there would be no difference between CR and IF on perceived eating behaviors, mood, sleep quality, quality of life (QOL) and cognition in women with overweight and obesity. In this prespecified secondary analysis of an open-label, single center, parallel assignment, randomized controlled trial, healthy women with overweight or obesity (N = 46, mean [SD] age 50 [9] years, BMI 32.9 [4.4] kg/m2), without a diagnosed eating disorder and who were randomized into 2 weight loss groups (prescribed 70% of calculated energy requirements as IF or CR) were included. Measurements were assessed in both IF and CR groups following a 12-hour overnight fast during baseline and week 8 and additionally following a 24-hour fast in the IF group only at week 8. We observed that IF produced greater weight and body fat loss than CR (P < .001). We did not detect any statistical difference between groups for the change in dietary restraint, disinhibition, hunger, mood, sleep quality, and QOL. An increase in cognitive performance was found in both IF (P = .036) and CR (P = .006) groups in one of the cognitive tasks, but there was no statistical difference between groups. Perceived eating behaviors, mood, sleep quality and cognitive performance were not changed by an acute 24-hour fast within the IF group (all P > .05). IF may be a viable alternative to CR for weight loss, in the short-term, without adversely impacting eating behaviors, mood, sleep quality, QOL or cognition in healthy women with overweight or obesity. However, larger and long term trials are required.
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Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet.
Napoleão, A, Fernandes, L, Miranda, C, Marum, AP
Nutrients. 2021;(4)
Abstract
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.
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Impact of intermittent vs. continuous energy restriction on weight and cardiometabolic factors: a 12-month follow-up.
Headland, ML, Clifton, PM, Keogh, JB
International journal of obesity (2005). 2020;(6):1236-1242
Abstract
BACKGROUND AND OBJECTIVE Intermittent energy restriction continues to gain popularity as a weight loss strategy; however, data assessing it's long-term viability is limited. The objective of this study was to follow up with participants 12 months after they had completed a 12-month dietary intervention trial involving continuous energy restriction and two forms of intermittent energy restriction; a week-on-week-off energy restriction and a 5:2 programme, assessing long-term changes on weight, body composition, blood lipids and glucose. SUBJECTS AND METHODS 109 overweight and obese adults, aged 18-72 years, attended a 12-month follow-up after completing a 12-month dietary intervention involving three groups: continuous energy restriction (1000 kcal/day for women and 1200 kcal/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (500 kcal/day on modified fast days each week for women and 600 kcal/day for men). The primary outcome was weight change at 24 months from baseline, with secondary outcomes of change in body composition, blood lipids and glucose. RESULTS For the 109 individuals who completed the 12-month follow-up (82 female, 15 male, mean BMI 33 kg/m2), weight decreased over time with no differences between week-on and week-off and continuous energy restriction or 5:2 and continuous energy restriction with -4.5 ± 4.9 kg for continuous energy restriction, -2.8 ± 6.5 kg for week-on, week-off and -3.5 ± 5.1 kg for 5:2. Total cholesterol reduced over time and glucose, HDL, LDL and triglycerides were unchanged. DISCUSSION AND CONCLUSION Intermittent energy restriction was as successful in achieving modest weight loss over a 24-month period as continuous energy restriction.
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Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study.
Pinto, AM, Bordoli, C, Buckner, LP, Kim, C, Kaplan, PC, Del Arenal, IM, Jeffcock, EJ, Hall, WL
Clinical nutrition (Edinburgh, Scotland). 2020;(6):1753-1763
Abstract
BACKGROUND & AIMS Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. METHODS This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. RESULTS Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P < 0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15 mmol/L (0.06, 0.24), P < 0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets. CONCLUSIONS Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.
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Markers of adipose tissue inflammation are transiently elevated during intermittent fasting in women who are overweight or obese.
Liu, B, Hutchison, AT, Thompson, CH, Lange, K, Heilbronn, LK
Obesity research & clinical practice. 2019;(4):408-415
Abstract
OBJECTIVE This study compared the effects of daily calorie restriction (DR) versus intermittent fasting (IF) on markers of inflammation and extracellular matrix deposition in adipose tissue and skeletal muscle in a controlled feeding trial in women with overweight or obesity. METHODS Women (N = 76) were randomised to one of three diets and provided with all foods at 100% (IF100) or 70% (IF70 and DR70) of calculated energy requirements for 8 weeks. IF groups ate breakfast prior to fasting for 24-h on 3 non-consecutive days/week. Weight, body composition, serum non-esterified fatty acids (NEFA), tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), M1- and M2-macrophage markers by qPCR and immunohistochemistry in adipose tissue and skeletal muscle were measured following a 12-h overnight fast (fed day, all groups) and a 24-h fast (IF groups only). RESULTS IF70 resulted in greater weight and fat losses and reductions in serum NEFA versus DR70 and IF100 (P < 0.05) after fed days. Markers of inflammation in serum (TNFα, IL6 and IL10), subcutaneous adipose tissue and skeletal muscle (CD68, CD40 and CD163) were unchanged by DR or IF after fed days. After fasting, NEFA, M1-macrophages (CD40+) in adipose tissue, and M2-macrophages (CD163+) in muscle were increased in IF70 and IF100 (all P < 0.05) and the changes in NEFA and mRNA of pan-macrophage marker CD68 in adipose tissue were positively correlated (r = 0.56, P = 0.002). CONCLUSIONS Unlike caloric restriction, IF transiently elevated markers of macrophage infiltration in adipose tissue and skeletal muscle, possibly in response to marked increases in adipose tissue lipolysis.
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Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.
Fitzgerald, KC, Vizthum, D, Henry-Barron, B, Schweitzer, A, Cassard, SD, Kossoff, E, Hartman, AL, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
Multiple sclerosis and related disorders. 2018;23:33-39
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Plain language summary
Multiple sclerosis (MS) is a disease of the central nervous system. Dietary modification is emerging as a safe intervention to potentially modify disease course. The main aim of this study was to assess the safety and feasibility of an intermittent fasting diet in people with MS. Secondary outcomes explored the effects of calorie restriction (CR) diets on body weight and anthropometric characteristics as well as on patient-reported outcomes including fatigue, sleep and mood. The study is a pilot randomised controlled feeding study of three different types of diets. Each participant (n=36) was randomized to 1 of 3 diets: a control diet (placebo), a daily CR diet and intermittent CR diet. Results indicate that daily CR diet was associated with marginally greater weight loss than the intermittent CR diet. Both CR diets were associated with trends toward improvements in cardiometabolic outcomes. Furthermore, CR diets were associated with in improvements in emotional well-being. Authors conclude that CR and weight loss represent interventions for clinically relevant symptoms due to MS, such as emotional well-being, without adding meaningful risks or adverse outcomes.
Abstract
An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.
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A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting (24 h/wk).
Kessler, CS, Stange, R, Schlenkermann, M, Jeitler, M, Michalsen, A, Selle, A, Raucci, F, Steckhan, N
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:143-152.e2
Abstract
OBJECTIVE The aim of the study was to evaluate whether intermittent fasting (IF) is an effective preventive measure, and whether it is feasible for healthy volunteers under every day conditions. METHODS A nonrandomized controlled clinical trial on IF was performed with healthy volunteers over a period of 8 wk, and a subsequent 4-mo follow-up. Outcomes were assessed at baseline, after 8 wk, and after 6 mo. Volunteers who were not interested in fasting served as a control group. Participants in the fasting group were asked to continue their regular nutritional habits on the nonfasting days, whereas the control group maintained their habitual nutrition throughout the whole period. Outcomes included changes of metabolic parameters (insulin, glucose, insulin resistance, insulin-like growth factor-1, brain-derived neurotropic factor, lipids, liver enzymes, hemoglobin A1c) and coagulation markers; bioelectrical impedance analysis; body mass index; abdominal girth; blood pressure; general quality of life (five-item World Health Organization Well-Being Index [WHO-5] questionnaire), as well as mood and anxiety (Hospital Anxiety and Depression Scale [HADS], Profile of Mood States, Flourishing-Scale, visual analog scale, Likert scales). The intervention consisted of a fasting day, which was repeated every week for 8 wk, with abstinence from solid food between 00:00 and 23:59 at minimum and a maximum caloric intake of 300 kcal on each fasting day. A per-protocol analysis was performed. P < 0.05 was considered significant. RESULTS Thirty-six volunteers were included; 22 allocated themselves to the fasting group, and 14 to the control group. Thirty-three data sets were included in the final analysis. Although significant in-group changes were observed in both groups for a number of outcomes after 8 wk and 6 mo, no significant between-group differences were observed for any outcome other than overall body fat mass after 8 wk as well as for the HADS total score and the WHO-5 total score after 6 mo, all in favor of the fasting group. However, none of the between-group differences were clinically relevant. CONCLUSIONS We did not find any clinically relevant differences between groups in this controlled clinical pilot trial of 8 wk of IF in healthy volunteers. Further clinical research in this field is warranted to further analyze mechanisms and effects of IF.
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Effect of Intermittent Compared With Continuous Energy Restricted Diet on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Noninferiority Trial.
Carter, S, Clifton, PM, Keogh, JB
JAMA network open. 2018;(3):e180756
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Abstract
IMPORTANCE Intermittent energy restriction is an alternative weight loss method that is becoming popular; however, to date, there are no long-term clinical trials of intermittent energy restriction in patients with type 2 diabetes. OBJECTIVE To compare the effects of intermittent energy restriction (2 days per week) with those of continuous energy restriction on glycemic control and weight loss in patients with type 2 diabetes during a 12-month period. DESIGN, SETTING, AND PARTICIPANTS Adult participants (N = 137) with type 2 diabetes were randomized 1:1 to parallel diet groups (intermittent energy restriction [n = 70] or continuous energy restriction [n = 67]) between April 7, 2015, and September 7, 2017, at the University of South Australia. Medications likely to cause hypoglycemia were reduced at baseline according to the medication management protocol. INTERVENTIONS An intermittent energy restriction diet (500-600 kcal/d) followed for 2 nonconsecutive days per week (participants followed their usual diet for the other 5 days) or a continuous energy restriction diet (1200-1500 kcal/d) followed for 7 days per week for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was change in hemoglobin A1c (HbA1c) level, with equivalence prespecified by a 90% CI margin of ±0.5%. The secondary outcome was weight loss with equivalence set at ±2.5 kg (±1.75 kg for fat mass loss and ±0.75 kg for fat-free mass loss). All other outcomes were tested for superiority. RESULTS Of the 137 randomized participants (77 women and 60 men; mean [SD] age, 61.0 [9.1] years; mean [SD] body mass index, 36.0 [5.8] [calculated as weight in kilograms divided by height in meters squared]; and mean [SD] HbA1c level, 7.3% [1.3%]), 97 completed the trial. Intention-to-treat analysis showed similar reductions in mean (SEM) HbA1c level between the continuous and intermittent energy restriction groups (-0.5% [0.2%] vs -0.3% [0.1%]; P = .65), with a between-group difference of 0.2% (90% CI, -0.2% to 0.5%) meeting the criteria for equivalence. Mean (SEM) weight change was similar between the continuous and intermittent energy restriction groups (-5.0 [0.8] kg vs -6.8 [0.8] kg; P = .25), but the between-group difference did not meet the criteria for equivalence (-1.8 kg; 90% CI, -3.7 to 0.07 kg), nor did the between-group difference in fat mass (-1.3 kg; 90% CI, -2.8 to 0.2 kg) or fat-free mass (-0.5 kg; 90% CI, -1.4 to 0.4 kg). There were no significant differences between groups in final step count, fasting glucose levels, lipid levels, or total medication effect score at 12 months. Effects did not differ using completers analysis. Hypoglycemic or hyperglycemic events in the first 2 weeks of treatment were similar between the continuous and intermittent energy restriction groups (mean number [SEM] of events, 3.2 [0.7] vs 4.9 [1.4]; P = .28), affecting 35% of participants (16 of 46) using sulfonylureas and/or insulin. CONCLUSIONS AND RELEVANCE Intermittent energy restriction is an effective alternative diet strategy for the reduction of HbA1c and is comparable with continuous energy restriction in patients with type 2 diabetes. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12615000383561.