COMPARISON OF INTERMITTENT AND CONTINUOUS CALORIE RESTRICTION STRATEGIES IN OVERWEIGHT AND OBESE PATIENTS.

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior, and hypothalamic gene expression.

Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional efficacy of intermittent CR to continuous CR in metabolic disorders such as diabetes. In this study, we analyzed two regimes of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2-5 or 5-9 regimes followed by free eating for 5 or 9 days respectively). In the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models. In conclusion, our study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving insulin sensitivity. Funding Statement: This study was supported by research grants from the National Natural Science Foundation of China (31630036 to Y.C.), the Ministry of Science and Technology of China (2016YFA0500103 to Y.C.), and the Chinese Academy of Sciences (XDA12010102, QYZDJ-SSW-SMC008, ZDRW-ZS-2016-8, and Y817X11141 to Y.C Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal experiments were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) with an approval number 2010-AN-8.

Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial

Intermittent fasting (IF) has gained attention for weight management and metabolic health, but detailed trials comparing its efficacy to calorie restriction (CR) in type 2 diabetes mellitus (T2D) are limited. Our aim was to compare the impact of CR diet with or without 12-hour overnight IF regimen on weight loss, glycemic control, and reduction of medication use in T2D. This was a 3-month, single-center randomized clinical trial. Participants (N = 99), 21-60 years with T2D, were randomly assigned to Group 1 (12-hour IF + CR, N = 48) or Group 2 (CR alone, N = 51). Anthropometric evaluations included weight, height, waist and hip circumference, and BMI. Body composition analysis was performed, and biochemical analysis included HbA1c, FBG, and fasting insulin levels to calculate the HOMA-IR. Physical activity was assessed using the Global Physical Activity Questionnaire. Both groups experienced significant weight loss after 12 weeks. The IF + CR group showed a more pronounced weight reduction (-6.51%) compared to the CR group (-4.41%) (P < 0.001) and significant improvements in HbA1c levels, with a reduction to 6.51% compared to 6.86% in the CR group (P = 0.035). The absolute reduction in HbA1c showed a significantly greater median decrease in the IF + CR group [-0.50 (IQR - 0.60 to -0.35)] compared with the CR group [-0.20 (IQR - 0.40 to -0.10)] (P = 0.002). IF + CR demonstrated significant reductions in waist circumference (-4.64%) and hip circumference (-3.12%) compared to the CR (-2.70% and -0.86%, respectively) (P < 0.05). Furthermore, IF + CR showed greater reductions in body fat mass (-9.39%) compared to the CR (-5.32%) (P < 0.001). Physical activity levels were comparable, with average MET of 100 and sedentary hours of 15.7 ( ± 3) for IF + CR and 16.2 ( ± 2.3) for CR, (P = 0.134). A 12-hour intermittent fasting (IF) regimen combined with calorie restriction (CR) demonstrated superior efficacy in promoting weight loss and improving glycemic control in patients with type 2 diabetes (T2D) compared to CR alone. Integrating IF into clinical nutrition guidelines could offer a practical and effective approach to diabetes management. The study was registered at the Pan African Clinical Trial Registry (PACTR202411524439559).

Although intermittent calorie restriction (ICR) has become popular as an alternative weight loss strategy to continuous calorie restriction (CCR), there is insufficient evidence on diet quality during ICR and on its feasibility over longer time periods. Thus, we compared dietary composition and adherence between ICR and CCR in a follow-up analysis of a randomized trial. A total of 98 participants with overweight or obesity [BMI (kg/m2) 25–39.9, 35–65 years, 49% females] were randomly assigned to ICR, operationalized as a “5:2 diet” (energy intake: ~100% on five non-restricted (NR) days, ~25% on two restricted (R) days), or CCR (daily energy intake: ~80%). The trial included a 12-week (wk) intervention phase, and follow-up assessments at wk24, wk50 and wk102. Apart from a higher proportion of energy intake from protein with ICR vs. CCR during the intervention (wk2: p < 0.001; wk12: p = 0.002), there were no significant differences with respect to changes in dietary composition over time between the groups, while overall adherence to the interventions appeared to be good. No significant difference between ICR and CCR regarding weight change at wk102 was observed (p = 0.63). However, self-reported adherence was worse for ICR than CCR, with 71.1% vs. 32.5% of the participants reporting not to or only rarely have followed the regimen to which they were assigned between wk50 and wk102. These results indicate that within a weight management setting, ICR and CCR were equivalent in achieving modest weight loss over two years while affecting dietary composition in a comparable manner.

Intermittent compared with continuous calorie restriction for treatment of metabolic dysfunction-associated steatotic liver disease: a randomized clinical trial

Pharmacokinetics of anaesthetic drugs at extremes of body weight

BackgroundIntermittent calorie restriction (ICR) is a novel method of dietary restriction for body weight control with the potential to improve obesity-related cardiometabolic markers, but the impact of this diet on subjects with hypertriglyceridemia (HTG) remains unknown.MethodsEighty-eight subjects with overweight or obesity and mild-to-moderate HTG were randomized to the continuous calorie restriction (CCR) group, or ICR group (a very low-calorie diet during 3 days of the week) for 8 weeks (44 patients in each group). Body composition, plasma lipids, glucose, insulin, adiponectin, and liver enzymes were measured at baseline and after 8 weeks. An intention-to-treat analysis was performed.ResultsThe body weight decreased in both groups (4.07 ± 1.83 kg in the CCR group and 4.57 ± 2.21 kg in the ICR group) with no significant difference between the groups. There was no significant difference between the two groups in the reduced amount of fat mass, fat-free mass, and waist circumference. Both groups achieved a significant reduction in plasma triglycerides after 8 weeks (by 15.6 and 6.3% in ICR and CCR groups, respectively) with no difference between treatment groups. HOMA-IR improved significantly in ICR compared to the CCR group (P = 0.03). Plasma glucose, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, liver enzyme, and adiponectin were not different between the two groups.ConclusionsThe results of this short-term study suggest that three-days a week of the ICR is comparable to a CCR diet for the reduction of triglycerides level in patients with HTG and in the short-term it appears to be more effective than continuous dieting in improving insulin resistance. However, longer-term studies are needed to confirm these findings.Trial registrationTrial registration number:NCT04143971.

BackgroundThe popularity of applying intermittent fasting (IF) has increased as more and more people are trying to avoid or alleviate obesity and metabolic disease. This study aimed to systematically explore the effects of various IF in humans.MethodsThe randomized controlled trials (RCTs) related to IF vs. non-intervention diet or caloric restriction (CR) were retrieved in PubMed, Web of Science, Cochrane Library database, and Embase. Extraction outcomes included, but were not limited to, weight, body mass index (BMI), waist circumference (WC), fasting glucose, and triglyceride (TG).ResultsThis study includes 43 RCTs with 2,483 participants. The intervention time was at least 1 month, and the median intervention time was 3 months. Contrasting results between IF and non-intervention diet showed that participants had lower weight (weighted mean difference (WMD) = 1.10, 95% CI: 0.09–2.12, p = 0.03) and BMI after IF (WMD = 0.38, 95% CI: 0.08–0.68, p = 0.01). The WC of participants after IF decreased significantly compared with the non-intervention diet (WMD = 1.02, 95% CI: 0.06–1.99, p = 0.04). IF regulated fat mass (FM) more effectively than non-intervention diet (WMD = 0.74, 95% CI: 0.17–1.31, p = 0.01). The fat-free mass of people after IF was higher (WMD = −0.73, 95% CI: (−1.45)–(−0.02), p = 0.05). There was no difference in fasting blood glucose concentrations between participants in the after IF and non-intervention diet groups. The results of insulin concentrations and HOMA-IR, though, indicated that IF was significantly more beneficial than non-intervention diet (standard mean difference (SMD) = −0.21, 95% CI: 0.02–0.40, p = 0.03, and WMD = 0.35, 95% CI: 0.04–0.65, p = 0.03, respectively). Cholesterol and TG concentrations in participants after IF were also lower than that after a nonintervention diet (SMD = 0.22, 95% CI: 0.09–0.35, p = 0.001 and SMD = 0.13, 95% CI: 0.00–0.26, p = 0.05, respectively). IF outcomes did not differ from CR except for reduced WC.ConclusionIntermittent fasting was more beneficial in reducing body weight, WC, and FM without affecting lean mass compared to the non-intervention diet. IF also effectively improved insulin resistance and blood lipid conditions compared with non-intervention diets. However, IF showed less benefit over CR.

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

The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial

To investigate the effects of different weight loss interventions on body mass index (BMI) and glucose and lipid metabolism in obese patients. Obese patients (n = 135) admitted to our hospital between December 2020 and August 2022 were divided into 3 groups, according to their diet patterns: calorie-restricted diet (CRD) group (n = 39), high-protein diet (HPD) group (n = 28), and 5 + 2 intermittent fasting (IF) group (n = 68). Body weight, body fat rate, BMI, hip circumference, and waist circumference were measured before and 60 days after implementation of the respective diet plan. Glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 2h postprandial blood glucose (2hPG), triglyceride (TG), total cholesterol, low-density lipoprotein, high-density lipoprotein, and adverse events were evaluated. Following the dietary intervention, the weight (P = .005 for CRD, P < .001 for HPD, and P = .001 for IF), body fat rate (P = .027 for CRD, P = .002 for HPD, and P = .011 for IF group), BMI (P = .017 for CRD, P < .001 for HPD, and P = .002 for IF group), hip circumference (P < .001 for CRD, P = .013 for HPD, and P = .032 for IF group), waist circumference (P = .005 for CRD, P < .001 for HPD, and P = .028 for IF group), HbA1c (P = .014 for CRD, P = .002 for HPD, and P = .029 for IF group), FBG (P = .017 for CRD, P < .001 for HPD, and P = .033 for IF group), and 2hPG (P = .009 for CRD, P = .001 for HPD, and P = .012 for IF group), were significantly decreased. TG (P = .007 for CRD, P < .001 for HPD, and P = .018 for IF group), TC (P = .029 for CRD, P = .013 for HPD, and P = .041 for IF group), LDL-C (P = .033 for CRD, P = .021 for HPD, and P = .042 for IF group), and LDL-C (P = .011 for CRD, P < .001 for HPD, and P = .027 for IF group) improved significantly in the 3 groups, when compared to that before treatment. The HPD had the best effect on reducing blood lipids, followed by the CRD; the effect of IF was slightly lesser. Short-term HPD, CRD, and IF can reduce the weight and body fat of overweight/obese individuals and improve blood lipid and blood sugar levels. The effect of HPD on weight loss, body fat, and blood lipid levels was greater than that of CRD or IF.

Context: Intermittent fasting (IF) and calorie restriction (CR) have gained interest as dietary strategies due to their potential for weight loss and multiple metabolic benefits. These strategies are often accompanied by exercise in an attempt to improve body composition and physical performance. However, further research is crucial to understanding whether or not physical performance is affected by the expected weight loss and related body composition changes in individuals on IF and CR, even when exercise is combined. Objective: We aimed to systematically evaluate the effects of IF and CR on exercise performance and body composition in adults aged 18 to 65 years. Data Source: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A systematic review was conducted up to April 2024 by searching electronic databases, including PubMed, Web of Science, and Scopus. There was no limit on publication dates. Data Extraction: The search explored the impact of IF and CR combined with exercise vs. exercise alone (control) on exercise performance outcomes: VO2max, handgrip strength, bench press strength, knee extensor strength, leg press strength, countermovement jump (CMJ), 400 m walk test, and gait speed; body weight, body mass index (BMI), and body composition: fat-free mass (FFM), fat mass (FM), and body fat percentage (BFP). Analyses included calculation of weighted mean difference (WMD), standardized mean difference (SMD), and 95% confidence intervals (CIs) to assess outcomes. Data Analysis: The meta-analysis included a total of 35 studies, ranging from 4 to 52 weeks and involving 1266 participants. The results showed that IF (hypocaloric or eucaloric diet) and CR combined with exercise increased handgrip strength [WMD = 1.707 kg, p = 0.01] compared to exercise alone. Moreover, IF and CR combined with exercise did not significantly affect VO2max [SMD = 0.005, p = 0.94], bench press strength [WMD = 0.377 kg, p = 0.778], knee extensor strength [WMD = −4.729 kg, p = 0.12], leg press strength [WMD = −2.874 kg, p = 0.415], countermovement jump [WMD = −0.226 cm, p = 0.80], 400 m walk test performance [WMD = −8.794 s, p = 0.06], or gait speed [WMD = 0.005 m/s, p = 0.82] compared to exercise alone. Moreover, IF and CR combined with exercise decreased body weight [WMD = −4.375 kg, p = 0.001], BMI [WMD = −1.194 kg·m−2, p = 0.001], FFM [WMD = −1.653 kg, p = 0.001], FM [WMD = −2.858 kg, p = 0.001], BFP [WMD = −0.826%, p = 0.001] compared to exercise alone. Conclusions: IF (hypocaloric or eucaloric) and CR can be effectively integrated into exercise training without negatively impacting most measures of physical performance, while significantly enhancing weight loss and adiposity-related outcomes. The findings from this meta-analysis involving both athletes and non-athletes suggest that weight loss induced by IF and CR combined with exercise does not necessarily result in reduced physical performance. In real-world scenarios, however, different outcomes are conceivable, as body composition, physical capacity, diet and exercise can vary considerably based on individual conditions.

BackgroundThe gut microbiota has been suggested to play a significant role in the development of overweight and obesity. However, the effects of calorie restriction on gut microbiota of overweight and obese adults, especially over longer durations, are largely unexplored.MethodsHere, we longitudinally analyzed the effects of intermittent calorie restriction (ICR) operationalized as the 5:2 diet versus continuous calorie restriction (CCR) on fecal microbiota of 147 overweight or obese adults in a 50-week parallel-arm randomized controlled trial, the HELENA Trial. The primary outcome of the trial was the differential effects of ICR versus CCR on gene expression in subcutaneous adipose tissue. Changes in the gut microbiome, which are the focus of this publication, were defined as exploratory endpoint of the trial. The trial comprised a 12-week intervention period, a 12-week maintenance period, and a final follow-up period of 26 weeks.ResultsBoth diets resulted in ~5% weight loss. However, except for Lactobacillales being enriched after ICR, post-intervention microbiome composition did not significantly differ between groups. Overall weight loss was associated with significant metabolic improvements, but not with changes in the gut microbiome. Nonetheless, the abundance of the Dorea genus at baseline was moderately predictive of subsequent weight loss (AUROC of 0.74 for distinguishing the highest versus lowest weight loss quartiles). Despite the lack of consistent intervention effects on microbiome composition, significant study group-independent co-variation between gut bacterial families and metabolic biomarkers, anthropometric measures, and dietary composition was detectable. Our analysis in particular revealed associations between insulin sensitivity (HOMA-IR) and Akkermansiaceae, Christensenellaceae, and Tanerellaceae. It also suggests the possibility of a beneficial modulation of the latter two intestinal taxa by a diet high in vegetables and fiber, and low in processed meat.ConclusionsOverall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction.Trial registrationThe trial, including the present microbiome component, was prospectively registered at ClinicalTrials.govNCT02449148 on May 20, 2015.

Introduction: High-frequency intermittent fasting (IF) diets reduce weight similarly to continuous calorie restriction (CR). In patients with type 2 diabetes, twice-weekly IF and CR equivalently reduced HbA1c. IF may improve chronic disease risk factors, but no controlled trial has evaluated whether IF reduces low-density lipoprotein cholesterol (LDL-C), regardless of weight loss, in patients with elevated LDL-C. Hypothesis: The Weekly ONe-Day watER-only Fasting interventionaL (WONDERFUL) randomized (1:1) controlled trial (NCT02770313) tested whether IF reduced LDL-C compared to ad libitum control over 6 months. Methods: Subjects (N=103) were ages 21-70 years, not taking a statin, had elevated baseline LDL-C (90-189 mg/dL for ages 21-39, 90-159 mg/dL for ages 40-70, ≥90 mg/dL for statin intolerant/contraindicated), and had diet-controlled type 2 diabetes or ≥1 metabolic syndrome feature but no anti-diabetes medication. The water-only IF regimen was 4 weeks of 2/week 24-hour IF followed by 22 weeks of 1/week 24-hour IF. Exclusions included pregnant, lactating, or chronic disease (e.g., CAD, MI, stroke/TIA, CKD, COPD, cancer, PE, PAD, DVT, dementia, type 1 diabetes). Results: At baseline, IF (n=50) and control (n=53) were, respectively, 49.3±12.0 and 47.0±9.8 years of age, 66.0% and 67.9% females, weight 103±24 and 100±21 kg, and LDL-C 124±19 and 128±20 mg/dL. Lost to follow-up (n=5 IF, n=4 control) and withdrawals (n=7 IF, n=16 control) gave a final sample of n=71 (n=38 IF, n=33 control). LDL-C change from baseline to 6 months was not different between IF and control (Table). HOMA-IR, one of 4 pre-specified secondary endpoints, was improved (-0.75 vs. -0.10) at p≤0.01 vs. control (Table). Conclusions: A once-per-week IF regimen did not reduce LDL-C compared to control, but HOMA-IR was significantly reduced. This more sustainable IF regimen may reduce some chronic cardiometabolic disease risks (e.g., HOMA-IR) with minimal effects on cholesterol and weight.