Intermittent Fasting vs Continuous Calorie Restriction for Weight Loss in Adults

Results 99 randomised clinical trials involving 6582 adults of varying health conditions (720 healthy, 5862 existing health conditions) were identified. All intermittent fasting and continuous energy restriction diet strategies reduced body weight when compared with ad-libitum diet. Compared with continuous energy restriction, alternate day fasting was the only form of intermittent fasting diet strategy to show benefit in body weight reduction (mean difference -1.29 kg (95% CI -1.99 to -0.59), moderate certainty of evidence). Additionally, alternate day fasting showed a trivial reduction in body weight compared with both time restricted eating and whole day fasting (mean difference -1.69 kg (-2.49 to -0.88) and -1.05 kg (-1.90 to -0.19), respectively, both with moderate certainty of evidence). Estimates were similar among trials with less than 24 weeks follow-up (n=76); however, moderate-to-long-term trials (≥24 weeks, n=17) only showed benefits in weight reduction in diet strategies compared with ad-libitum. Furthermore, in comparisons between intermittent fasting strategies, alternate day fasting lowered total cholesterol, triglycerides, and non-high density lipoprotein compared with time restricted eating. Compared with whole day fasting, however, time restricted eating resulted in a small increase in total cholesterol, low density lipoprotein cholesterol, and non-high density lipoprotein cholesterol. No differences were noted between intermittent fasting, continuous energy restriction, and ad-libitum diets for HbA 1c and high density lipoprotein. Conclusions Minor differences were noted between some intermittent fasting diets and continuous energy restriction, with some benefit of weight loss with alternate day fasting in shorter duration trials. The current evidence provides some indication that intermittent fasting diets have similar benefits to continuous energy restriction for weight loss and cardiometabolic risk factors. Longer duration trials are needed to further substantiate these findings.

Conclusions Our network meta-analysis showed similar benefits for various intermittent fasting strategies and CER in cardiometabolic risk compared with ad-libitum diets. ADF presented additional trivial to moderate improvements to CER in overall weight, anthropometric measurements, lipid, and systolic blood pressure measures; however, this benefit was not observed in other intermittent fasting strategies. In relation to body weight, ADF showed a reduction when compared with CER, and TRE in shorter trials, although benefits of any diet strategies were lost in longer duration studies. The current evidence provides some indication of the benefits for caloric restriction and intermittent fasting diets, with little additional benefit for intermittent fasting, in cardiometabolic risk. Additional high quality randomised clinical trials with extended durations beyond 52 weeks are needed to elucidate the long term effects of these dietary strategies, with greater emphasis between intermittent fasting diets, and their impact on cardiometabolic health and cardiovascular outcomes across diverse populations.

When compared with the ad-libitum diet, the network analysis showed a small reduction in body weight for ADF (mean difference -3.40 kg (95% CI -4.14 to -2.67), high certainty of evidence), WDF (-2.36 kg (-3. 02 to -1.70), high certainty of evidence), and CER (-2.11 kg (-2.73 to -1.50), moderate certainty of evidence); while TRE showed a trivial reduction (-1.72 kg (-2.21 to -1.22), moderate certainty of evidence) (fig 3). Furthermore, the ADF diet resulted in a trivial additional weight loss when compared with CER (-1.29 kg (-1.99 to -0.59), moderate certainty of evidence). Comparisons between intermittent fasting diet strategies showed a trivial reduction in body weight for ADF versus both TRE (-1.69 kg (-2.49 to -0.88) and WDF -1.05 kg (-1.90 to -0.19), both moderate certainty of evidence); however, no difference was noted between the TRE and WDF diet comparison (fig 3).

No significant differences were found between the IER and CER diet for changes in body weight (WMD: -0.42 kg; 95% CI: -0.96 to 0.13; k = 25; P = 0.132; Supplementary Figure 1A) and BMI (WMD: -0.03; 95% CI: -0.30 to 0.24; k = 13; P = 0.814; Supplementary Figure 1B). The TRE diet showed a greater weight loss than CER diet (WMD: -0.93 kg; 95% CI: -1.69 to -0.17; k = 6; P = 0.016), whereas ADF and the 5:2 diet achieved a comparable weight loss as the CER diet. BMI was reduced less in the 5:2 diet group compared with the CER diet group (WMD: 0.34; 95% CI: 0.04-0.64; k = 4; P = 0.025).

The intermittent approach determined a comparable weight-loss (WMD: - 0.61 kg; 95% CI - 1.70 to 0.47; p = 0.87) or percent weight loss (WMD: - 0.38%, - 1.16 to 0.40; p = 0.34) when compared to the continuous approach.

Eleven RCTs 13 , 14 , 16 , 17 , 21 , 22 , 25, 26, 27, 28, 29 were analyzed to compare the effects of IF and ER on baseline weight change. The random effects model (Figure 3) illustrated the effectiveness of IF, revealing a slightly greater, though statistically nonsignificant, weight decrease than observed for ER (MD [95 % CI]: -0.41 [-1.25 to 0.42]; p = 0.33). Furthermore, sensitivity analysis demonstrated that none of the included studies affected the overall estimate for this outcome (Supplementary Fig. 3).

The changes in body weight (WMD, -0.06; 95% CI, -0.18 to 0.05), WC (WMD, -0.12; 95% CI, -0.28 to 0.05), and body fat percentage (WMD, -0.14; 95% CI, -0.34 to 0.05) did not differ significantly between the two intervention groups (Fig. 2A, C, and E); significant differences in those values were not found even in the subgroup analyses for types of IER (Fig. 2A, C, and E) and measurement time points (Fig. 2B, D, and F).

Compared to regular dietary advice, intermittent fasting may result in little to no difference in percentage from baseline weight loss (MD -0.33, 95% CI -0.92 to 0.26; 21 studies, 1430 participants; low-certainty evidence due to risk of bias). Intermittent fasting may have little to no effect on achieving a 5% reduction in body weight, but the evidence is very uncertain (RR 0.98, 95% CI 0.82 to 1.18; 4 studies, 472 participants; very low-certainty evidence due to risk of bias and imprecision). Intermittent fasting may result in little to no difference in quality of life (SMD 0.11, 95% CI -0.27 to 0.49; 3 studies, 106 participants; low-certainty evidence due to risk of bias and imprecision). Intermittent fasting may have little to no effect on adverse events but the evidence is very uncertain (RR 1.45, 95% CI 0.64 to 3.28; 7 studies, 619 participants; very low-certainty evidence due to risk of bias, inconsistency and imprecision).

Traditional dietary advice includes reducing calories, and changing eating habits to eat healthier foods or different amounts of protein, carbohydrate and fat.

We included randomised controlled trials (RCTs) and cluster-RCTs that compared intermittent fasting (including time-restricted feeding, periodic fasting, alternate-day fasting, and modified alternate-day fasting) with regular dietary advice, no intervention or waiting list in men and women with overweight or obesity, with or without associated comorbid conditions. The minimum duration of the intervention was four weeks, and the minimum duration of follow-up was six months. We excluded cross-over and quasi-RCTs.

Results: This review included 11 RCTs (n = 850). Meta-analysis showed that IER had greater effects on absolute weight loss, the percentage of weight loss, and improving insulin sensitivity than CER. In the subgroup analysis, short-term (2-3 months) intervention (P < 0.0001) was associated with weight loss.

We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger’s test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = -0.21, 95% CI (-0.40, -0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (-0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects.

In trials with less than 24 weeks of follow-up (n=76), ADF showed a small body weight reduction compared with ad-libitum (mean difference -3.37 kg (95% CI -4.16 to -2.59)), and a trivial reduction in weight compared with CER (-1.29 kg (-2.05 to -0.53)), and TRE (-1.72 kg (-2.58 to -0.87)).

In trials of 24 weeks or more (n=17), the most restrictive strategies (ADF, TRE, and CER) showed small body weight reductions versus ad-libitum (mean difference range -1.88 to -3.63 kg), with no differences between intermittent fasting strategies and CER in these moderate-to-long term studies. WDF, however, showed a trivial reduction in weight loss when compared with ad-libitum.

Nine out of the ten studies assessed focused on ponderal weight loss in obese patients who underwent interventions lasting less than six months [22,23,24,25,26,27,28,29,30]. The short-term effects of FBS on body weight is illustrated in Figure 3A. Both interventions led to weight loss, with a reduction of 5.5 to 6.5 kg observed at the six-month mark. However, the combined analysis of the nine studies (n = 565) revealed a statistically significant (p = 0.004) overall effect size (-0.94 kg [95% CI: -1.58, -0.31], indicating that FBS were more effective than CCR to reduce body weight. Although there was moderate heterogeneity (I 2 = 42%), this variability was not statistically significant (p = 0.08).

Interestingly, when weight loss interventions are planned to extend beyond six months, the overall effects tend to disappear, as illustrated in Figure 3B. The results were consistent (I 2 = 12%) across the five studies (n = 423), and the overall effect of the fasting-based interventions compared to CCR on body weight loss was not statistically significant (0.06 kg [95% CI: -0.98, 1.09], p = 0.34) [21,23,24,28,30].

The subgroup that only included trials with a duration of <13 wk showed significantly greater decreases in body weight (WMD: -0.75 kg; 95% CI: -1.24 to -0.25; k = 12; P = 0.003) in IER compared with CER (Supplementary Table 8). The subgroup that only contained studies with a duration of >13 wk showed that the decrease in WC was significantly larger in IER than in CER (WMD: -1.28 cm; 95% CI: -2.42 to -0.15; k = 7; P = 0.026).

Owing to the high heterogeneity, we performed subgroup analysis for intervention duration (≤4, 4-12, and >12 weeks). We found more weight loss with longer intervention duration (-0.75 vs. -1.12 kg), but not for intervention duration longer than 12 weeks. This could mean that IER reduced more BW than CER when the intervention duration was less than 12 weeks, but there was no significant difference between IER and CER when the intervention duration was longer than 12 weeks. We found a similar trend for FFM (Table 4).

Results: Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group.

In total 112 participants (men [50%] and women [50%]) aged 21-70 years with BMI 30-45 kg/m 2 (mean 35.2 [SD 3.7]) were randomized to intermittent or continuous energy restriction.

Weight loss was similar among participants in the intermittent and continuous energy restriction groups (8.0 kg [SD 6.5] versus 9.0 kg [SD 7.1]; p=0.6).

Weight regain was minimal and similar between the intermittent and continuous energy restriction groups (1.1 kg [SD 3.8] versus 0.4 kg [SD 4.0]; p=0.6).

Weight change at wk102 after baseline was slightly, but not significantly lower with ICR than CCR (-4.3% ± 1.0% vs. -5.0% ± 1.1%).

Of the total 139 participants who underwent randomization, 118 (84.9%) completed the 12-month follow-up visit. The mean weight loss from baseline at 12 months was -8.0 kg (95% confidence interval [CI], -9.6 to -6.4) in the time-restriction group and -6.3 kg (95% CI, -7.8 to -4.7) in the daily-calorie-restriction group. Changes in weight were not significantly different in the two groups at the 12-month assessment (net difference, -1.8 kg; 95% CI, -4.0 to 0.4; P=0.11). Results of analyses of waist circumferences, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome. In addition, there were no substantial differences between the groups in the numbers of adverse events.

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] HbA 1c level, 7.3% [1.3%]), 97 completed the trial. Intention-to-treat analysis showed similar reductions in mean (SEM) HbA 1c 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).

Both groups lost significant weight between baseline and 3 months, which was maintained at 12 months (mean [SEM] weight reduction from 3 to 12 months was 0.4 [0.5] kg in the continuous energy restriction group and -0.2 [0.6] kg in the intermittent energy restriction group; P = .48).

Background: Long-term (≥12 months) randomized trials evaluating the efficacy of intermittent fasting (IMF) as a dietary weight loss strategy are limited. Further, no studies have compared IMF to daily caloric restriction (DCR) when both interventions are provided in the context of a guidelines-based behavioral weight loss program. Objective: To compare the effects of 4:3 IMF to DCR on changes in weight at 12 months, with comprehensive behavioral support provided to both groups. Design: Randomized clinical trial (NCT03411356). Setting: Denver, Colorado and surrounding metropolitan area. Participants: Adult (age 18-60 years) participants with BMI 27-46 kg/m 2. Interventions: IMF was instructed to restrict energy intake by 80% on three non-consecutive days/week with ad libitum intake (no restriction) the other four days (4:3 IMF). DCR was instructed to reduce daily energy intake by 34% to match the weekly energy deficit of 4:3 IMF. Both groups received a high-intensity comprehensive behavioral weight loss program including group-based behavioral support and a recommendation to increase moderate-intensity physical activity to 300 minutes/week. Measurements: The primary outcome was change in body weight (kg) at 12 months. Results: Of the 165 (4:3 IMF, n=84; DCR, n=81) randomized participants (mean±SD; age 42±9 years, BMI 34.1±4.4 kg/m 2, 73.9% female), 125 completed the trial. In an intent-to-treat analysis, 4:3 IMF demonstrated greater reductions in weight (mean (95% CI); -2.89 kg (-5.65, -0.14 kg); P=0.03) vs DCR at 12 months. Limitations: Limited generalizability. Conclusion: Compared to DCR, 4:3 IMF produced modestly greater weight loss among adults with overweight or obesity enrolled in a 12-month high-intensity comprehensive behavioral weight loss program.

At 12 months, percent change in body weight from baseline was -7.6% (-9.5%, -5.7%) in 4:3 IMF and -5.0% (-6.9%, -3.1%) in DCR. Fifty-eight percent (n=50) of 4:3 IMF achieved ≥5% weight loss at 12 months vs forty-seven percent (n=27) of DCR participants. Thirty-eight percent (n=26) of 4:3 IMF achieved ≥10% weight loss at 12 months vs sixteen percent (n=9) of DCR participants. Changes in body composition, BMI, and WC also tended to favor 4:3 IMF, although estimates were imprecise (Figure 2 and Supplementary Table S5).

The 2 RCTs including longer follow-ups (24 months) did not find between-arms differences in weight loss maintenance [17, 27]. Studies with longer follow-ups, evaluating the long-term sustainability, adherence to, and safety of IER regimens are needed.

Eight RCTs involving 579 participants were enrolled in the present analysis. The pooled results showed that TRE with CR reduced the body weight, fat mass, and waist circumference significantly (WMD: -1.40, 95% CI: -1.81 to -1.00, and I 2 : 0%; WMD: -0.73, 95% CI: -1.39 to -0.07, and I 2 : 0%; WMD: -1.87, 95% CI: -3.47 to -0.26, and I 2 : 67.25%, respectively). However, compared with CR alone, TRE plus CR exhibited no significant benefit on the blood pressure, glucose profile, and lipid profile.

Subgroup analysis was conducted based on different durations to investigate the long-term effects of combined TRE and CR. The results showed that the body weight was reduced in participants who received a long-term period (>12 weeks) of intervention (WMD: -1.46, 95% CI: -1.89 to -1.03, and I 2 : 0%; Table 2), but a nonsignificant decrease was observed in those who were scheduled for short-term intervention duration (<12 weeks).

The GRADE evaluation rated six of the twelve outcomes from the current study as low quality, and the remaining six were classified as very low quality.

In studies that used isocaloric control strategies, the TRE group showed significant reductions in BW (MD: -1.46 kg; 95% CI: -2.65, -0.26), FM (MD: -1.50 kg; 95% CI: -2.77, -0.24), and FFM (MD: -0.41 kg; 95% CI: -0.79, -0. 03).

Data extraction: We included 30 studies involving a total of 1341 participants. Studies were screened based on titles and abstracts followed by full-text reading, and data were extracted from eligible studies using a pre-established form. All these steps were performed by 2 authors independently and blinded, with discrepancies resolved by a third author.

Both the eTRE+ER group (-6.3 kg [-5.7%]; 95% CI, -7.4 to -5.2 kg; P < .001) and CON+ER group (-4.0 kg [-4.2%]; 95% CI, -5.1 to -2.9 kg; P < .001) achieved clinically meaningful weight loss (Figure 3). The eTRE+ER group lost an additional 2.3 kg of body weight (95% CI, -3.7 to -0.9 kg; P = .002) relative to the CON+ER group. However, there were no statistically significant differences in absolute fat loss (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (n = 41; -4.2%; 95% CI, -14.9 to 6.5%; P = .43). There were also no statistically significant differences in the changes in fat-free mass, trunk fat, visceral fat, waist circumference, or appendicular lean mass (Table 2).

Of note, a somewhat larger study recently published in the New England Journal of Medicine by Liu et al 53 reported that eTRE was not better for losing weight. However, our study had better post hoc statistical power owing to less variability in weight loss. Our 95% CI was narrower than and wholly contained within the other trial’s 95% CI. Therefore, our results are not incompatible. Furthermore, our eTRE group extended their daily fasting by twice as much, fasting an extra 4.8 hours per day vs only a modest 2.3-hour change in the Liu et al 53 study.

Meta-regression analyses have shown that weight loss was similar when IF regimens were compared with CER (mean difference: 0.26 kg, 95% CI: -0.31 to 0.84; p = 0.37; Figure 3). The moderate mean differences of loss of body weight observed were similar when comparing the ADF/MADF regimen with CER diets and were not statistically significant (0.17 kg, 95% CI: -0.69 to 1.03; p = 0.70) or the 5:2 diet to CER (0.22 kg, 95% CI: -0.66 to 1.09; p = 0.63).

To our knowledge, this is the first randomized, controlled, long-term study of the 5:2 approach to intermittent fasting indicating that intermittent energy restriction is as effective, but not superior to continuous energy restriction at inducing clinically significant weight loss (2) and maintenance and improving cardiometabolic risk factors in free-living men and women with abdominal obesity and at least one additional component of metabolic syndrome.

Conclusions and relevance: Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.

4:3 IMF demonstrated greater percent caloric restriction vs DCR over the initial 6 months of the intervention (-14.25 (-17.21, -11.28%) vs -10.20 (-12.67, -7.74%)) and over the entire 12-month intervention (-9.75 (-12.83, -6.68%) vs -5.64 (-8.04, -3.24%)). However, both groups were below the targeted weekly energy defect of 34.3%.

We identified one additional study which compared ADF to DCR over 1 year with a matched targeted energy deficit (10). All five studies (6-10) showed no difference in weight loss between the IMF paradigm studied and DCR, however there were some limitations.

This meta-analysis compared the effects of these IER diets with continuous energy restriction (CER) on anthropometrics and cardiometabolic risk markers in healthy adults. Twenty-eight trials were identified that studied TRE (k = 7), ADF (k = 10), or the 5:2 diet (k = 11) for 2-52 wk. Energy intakes between intervention groups within a study were comparable (17 trials), lower in IER (5 trials), or not reported (6 trials).

When interpreting the results, it is important to realize that decreases in energy intake during the intervention periods between the IER and CER groups were not comparable in all included studies, which makes it difficult to compare the specific diets without the influence of differences in energy intake.

To what extent differences in energy intakes between groups within studies may have influenced these outcomes should be addressed in future studies.

It could be hypothesized that the very low caloric intake on “fast” days determined an overall lower caloric intake in the IER arms, which were therefore difficult to be compared with the CER arms. In the only RCT where water and calorie-free beverages were allowed in the “fast” days, a significant between-arms difference in energy intake was evident [27]; in two studies a between-arms difference of 300-400 kcal was observed [22, 23] while most RCTs reported a negligible between-arms difference (~ 100 kcal) [17, 20, 21, 25, 26].

Both groups reported reductions in average weekly energy and macronutrient intakes, however the IER group reported greater reductions for average daily intake of energy (mean difference between groups [95% CI] -716 [-1240 to -192] kJ, -9 [-14 to -2] %, P<0.01), protein (-5.5 [-10.0 to -0.8] g, -6 [-13.0 to 0.0] %, P=0.02) and carbohydrate (-24 [-41 to -8] g, -11 [-18 to -3] %, P=0.004).

It is worth noting that the self-reported caloric intake in the included studies showed that participants in the IF group consumed slightly fewer calories than those in the CR group

There were no between-group differences in self-reported physical activity, energy intake (1 kcal/d; 95% CI, -251 to 253 kcal/d; P = .99), or macronutrient composition (eTable 2 in Supplement 1). However, weight-loss modeling 42 of all participants with at least 2 weight measurements (n = 77) indicated that eTRE reduced energy intake by an additional 214 kcal/d (95% CI, -416 to -12 kcal/d; P = .04) relative to the control eating window.

In this 12-month trial, we found that the 8-hour time-restricted-eating regimen did not produce greater weight loss than the regimen of daily calorie restriction, with both regimens resulting in similar caloric deficits. In addition, time-restricted eating and daily calorie restriction produced similar effects with respect to reductions in body fat, visceral fat, blood pressure, glucose levels, and lipid levels over the 12-month intervention period. These results indicate that caloric intake restriction explained most of the beneficial effects seen with the time-restricted-eating regimen.

Of the 1,438 participants in 16 RCTs randomized to the CER and IER groups, 1,074 participants finished the active weight-loss intervention, for an attrition rate of 25.3%. The attrition rates were 26.6% and 24.1% for the IER and CER groups, respectively.

IER can be used as an alternative to CER because it induces comparable weight loss and metabolic improvement. However, the effect of IER was not superior to that of CER, and its attrition rate was not lower than that of CER.

The total number of subjects included in the present analysis was 630 at enrolment. During the course of the trials, 102 patients dropped out. Drop-out rates ranged from about 2% [21] to 38% for IER arms [22] and from 0% [23] to 50% [22] for CER. The number of participants analyzed at the end of the RCTs was 528.

The incidence of attrition at 12 months was 19.0% in 4:3 IMF and 29.6% in DCR.

One hundred twenty-one participants were randomized to the clinical trial, and 62 participants completed the trial to 12 months (49% attrition). Withdrawal was similar between both diet groups (IER 48% (n = 29), CER 50% (n = 30), p = 0.8).

Intermittent restriction participants reported higher hunger scores than continuous restriction participants on a subjective numeric rating scale (4.7 [SD 2.2] vs 3.6 [SD 2.2]; p=0.002).

Regarding hunger levels, four studies used the visual analogue scale (VAS). The results indicated that hunger levels were significantly lower in the CR group (standardized mean difference [SMD] = 0.37, 95 % confidence interval [CI]: 0.12, 0.62, P = 0.003). Quality-of-life was assessed by recording the occurrence of side effects reported by the participants. There was a significant reduction in fatigue (odds ratio [OR] = 1.79, 95 % CI: 1.03, 3.09, P = 0.04) and total events of side effects in the control group compared to the intervention group (OR = 1.51, 95 % CI: 1.14, 2, P = 0.004) as shown in (Supplementary Fig. 4). Finally, there was no significant difference in the number of dropouts at any time point (Supplementary Fig. 5).

At the end of the trial 31 of IER (58%) and 46 (85%) of CER subjects planned to continue the diet allocated at randomisation.

When asked whether they had continued with the diets initially assigned to them between the end of the active study (wk50) and the telephone follow-up (wk102), 71.1% of the participants in the ICR group reported that they had not at all or only rarely done so, compared to 32.5% in the CCR group (p< 0.001, Table S6).

Overall compliance to both diets was excellent during the first 3 months of treatment (90% in the continuous energy restriction group and 97% in the intermittent energy restriction group; P = .21), after which the compliance rates decreased in both groups (49% in the continuous energy restriction group and 44% in the intermittent energy restriction group; P = .62).

For the short-term studies, percentage adherence ranged from 71.7% to 98% for ADF/MADF, 73.5% to 98% for the 5:2 diet, and 83% to 89% for TRE. In the longer-term studies (>3 months), adherence was generally lower than for the short-term studies, ranging from 8% [16] to 73% [28].

Weighted mean differences (WMDs) were calculated using fixed- or random-effects models. Changes in body weight [WMD: -0.42 kg; 95% confidence interval (CI): -0.96 to 0.13; P = 0.132] and fat mass (FM) (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; P = 0.362) were comparable when results of the 3 IER diets were combined and compared with those of CER. All IER diets combined reduced fat-free mass (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; P = 0.044) and waist circumference (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; P = 0.036) more than CER.

Effects on body mass index [BMI (kg/m 2)], glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), serum lipid and lipoprotein concentrations, and blood pressure did not differ. Further, TRE reduced body weight, FM, and fat-free mass more than CER, whereas ADF improved HOMA-IR more. BMI was reduced less in the 5:2 diet compared with CER.

The IER regimen resulted in a significantly greater WC reduction than the CER regimen (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; k = 17; P = 0.036; Supplementary Figure 1C). No significant effects on WC were found for the 3 IER diets separately (P> 0.05). Relevant heterogeneity between studies was found for body weight, BMI, and WC (I 2> 50%).

FFM decreased more in the IER diet groups than in the CER diet group (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; k = 16; P = 0.044, Supplementary Figure 1D) and no relevant heterogeneity was observed (I 2 = 39.7%). No overall effect was found for FM (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; k = 15; P = 0.362; Supplementary Figure 1E), and heterogeneity was relevant (I 2 = 74.9%). The changes in FFM and FM were significantly greater for TRE than that for CER (FFM: WMD: -0.34 kg; 95% CI: -0.67 to -0.01; k = 5; P = 0.042 | FM: WMD: -0.91 kg; 95% CI: -1.63 to -0.18; k = 4; P = 0.014). These significant subgroup effects were not observed for ADF and the 5:2 diet.

Changes in fasting TG (WMD: -0.01 mmol/L; 95% CI: -0.07 to 0.04; k = 17; P = 0.673; Supplementary Figure 2A), TC (WMD: -0.03 mmol/L; 95% CI: -0.11 to 0.05; k = 16; P = 0.604; Supplementary Figure 2B), HDL cholesterol (WMD: -0.001 mmol/L; 95% CI: -0.03 to 0.02; k = 16; P = 0.934; Supplementary Figure 2C), and LDL cholesterol concentrations (WMD: -0.04 mmol/L; 95% CI: -0.10 to 0.02; k = 16; P = 0.162, Supplementary Figure 2D) were not significantly different between IER and CER. Relevant heterogeneity was not observed for TG, TC, HDL cholesterol, and LDL cholesterol (I 2< 50%). Effects on fasting TG, TC, HDL cholesterol, and LDL cholesterol concentrations did not differ between the TRE, ADF, and 5:2 subgroups compared with CER (P> 0.05).

Comparable changes were observed between IER and CER for fasting glucose concentrations (WMD: -0.01 mmol/L; 95% CI: -0.08 to 0.05; k = 19; P = 0.681; Supplementary Figure 3A), fasting insulin concentrations (WMD: -0.17 μIU/mL; 95% CI: -0.82 to 0.47; k = 14; P = 0.604; Supplementary Figure 3B) and HOMA-IR (WMD: -0.07; 95% CI: -0.22 to 0.08; k = 13; P = 0.338; Supplementary Figure 3C). No heterogeneity was present for these outcomes (I 2< 50%). When analyzed separately, TRE, ADF, and the 5:2 diet did not show significantly different changes in glucose and insulin concentrations compared with the CER diet, whereas HOMA-IR decreased more in ADF than in CER (WMD: -0.73; 95% CI: -1.43 to -0.03; k = 4; P = 0.042).

Changes in SBP and DBP did not significantly differ between IER and CER (SBP: WMD: -0.48 mm Hg; 95% CI: -1.64 to 0.69; k = 15; P = 0.423 | DBP: WMD: -0.67 mm Hg; 95% CI: -2.05 to 0.71; k = 14; P = 0.342; Supplementary Figure 4). Relevant heterogeneity was found for DBP (I 2 = 59.2%) and not for SBP. In agreement with the overall effects of SBP and DBP, none of the separate IER diets differed significantly from the CER diet (P> 0.05).

Similar beneficial results in body weight were observed for intermittent fasting strategies with ad-libitum diets for other body measurements including BMI, body fat, and waist circumference. Among these measurements, ADF showed a large reduction in BMI when compared with ad-libitum (mean difference -1.22 (95% CI -1.55 to -0.89), high certainty of evidence); however, reductions in waist circumference were small (high certainty of evidence) and in body fat were trivial (moderate certainty of evidence). Additionally, moderate reductions in BMI were observed in ADF with WDF (-0.53 (-0.94 to -0.13)) and TRE (-0.60 (-0.97 to -0.24)), with moderate certainty of evidence (fig 5, supplementary figure 4). Furthermore, ADF showed reductions in both BMI (-0.52 (-0.85 to -0.19)) and waist circumference (-1.19 cm (-2.13 to -0.24)), when compared with CER, both with moderate certainty of evidence.

Five RCTs assessed waist circumference [20-23, 26] without showing any differences between arms (WMD: - 0.17 cm; 95% CI - 1.74 to 1.39; p = 0.83).

For body fat mass, data from eight studies (n = 453) revealed a statistically significant (p = 0.0001) reduction favoring the fasting group (-1.08 kg [95% CI: -1.63, -0.53]) [22,23,24,25,26,27,29,30]. However, the effects on waist circumference (n = 502) and hip circumference (n = 233) were not significantly different from the CCR group.

A meta-analysis of 10 studies that measured blood glucose levels showed that the change in blood glucose levels was in favor of CER and not IER (WMD, 0.16; 95% CI, 0.02-0.30), and the same result was found in the subgroup analysis of measurement time points for 8-12 weeks (WMD, 0.20; 95% CI, 0.04-0.36) (Fig. 3A and B). The superior effect of CER to IER on glucose levels was not observed at measurement time points of 16-24 weeks and 52 weeks (Fig. 3B). However, there was significant heterogeneity in the effect sizes of changes in blood glucose levels (chi 2=58.25, P<0.01, I 2=85%) (Fig. 3A).

Excluding those four trials did not produce changes in the significance of any of the analyses except SBP. Without those four trials, the overall differences in SBP changes became insignificant between the two diet interventions (WMD, 0.15; 95% CI, -0.01 to 0.31). In the sensitivity analysis for blood glucose level, the leave-one-out method was used because the overall I 2 heterogeneity was high. In the absence of outliers, the overall differences in glucose level changes became insignificant between the two diet interventions (WMD, 0.04; 95% CI, -0.11 to 0.19).

SBP was significantly lower in the CER group than the IER group after the intervention (WMD, 0.21; 95% CI, 0.05-0.36) (Fig. 4A). However, DBP did not differ significantly between the groups, except for the results of the subgroup analysis for TRE, which was in favor of CER (WMD, 0.47; 95% CI, 0.10-0.83) (Fig. 4C). According to the measurement time points, no significant differences were found in SBP and DBP changes between the groups (Fig. 4B and D). In the sensitivity analysis of studies without an overall high risk of bias, no significant difference was found in the SBP changes between the groups (WMD, 0.15; 95% CI, -0.01 to 0.31; not shown in figures).

On the contrary, fasting insulin values were significantly reduced with IER (WMD = - 0.89 µU/mL; 95% CI - 1.56 to - 0.22; p = 0.009; I 2 = 0%) and the estimated effect appeared robust in the leave-one-out sensitivity analysis (data not shown).

The difference we found (- 0.89 µU/mL) was statistically significant, but not clinically relevant, above all considering the fact that participants to the included RCTs were overweight/obese and therefore probably insulin-resistant individuals.

The assessment of all diet strategy comparisons showed no association with HbA 1c or high density lipoprotein cholesterol; certainty of evidence ranged from low to high (supplementary figures 10 and 11). Conversely, all diet strategies showed a trivial decline in fasting glucose and HOMA-IR when compared with ad-libitum diet; evidence was of moderate certainty (supplementary figures 8 and 12).

There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.

Both time-restricted eating and daily calorie restriction were associated with reduced systolic and diastolic blood pressure over 12 months, with no substantial between-group differences (Table 3 and Table S6). Fasting glucose levels, 2-hour postprandial glucose levels, scores on the insulin disposition index and HOMA-IR, and lipid levels were similar in the two groups during the 12 months of the trial.

Overall, the loss in body weight may be more important for improvements in cardiometabolic risk markers than the type of diet used to reach that weight loss.

In conclusion, we observed that ADF and CR similarly increased the FFM:total mass ratio, decreased circulating leptin, and did not affect the VAT:SAT ratio or our other measured adipokines. Weight loss, rather than the pattern of ER, appeared to be the main driver of these changes; and weight loss greater than 8% may be needed to elicit changes in levels of circulating adipokines other than leptin.

Overall, included participants had a median age of 45 years (interquartile range 36-50), had overweight or obesity (median BMI of 31.3 (interquartile range 28.4-33.3)), and were mostly female (66% female, 34% male) (total n=6582). The participants had varying health conditions, including having overweight or obesity (54 studies), type 1 diabetes or type 2 diabetes (12 studies), metabolic syndrome (8 studies), or metabolic dysfunction-associated fatty liver disease (also known as non-alcoholic fatty liver disease; 8 studies); overall, 720 individuals were healthy and 5862 had existing health conditions.

The high variability among the RCTs in the feeding protocols, the limited follow-up, the small sample sizes, the high drop-out rates potentially leading to selection bias, the limited reporting of adverse events and blinding of investigators about arm allocation, or other methodological problems are all limitations to be considered. Finally, most studies were performed by the same authors and the majority of subjects included were adult healthy women, thus limiting the generalizability of the results.

Equivalence was demonstrated for change in HbA 1c level; however, given the large variability in weight reduction, equivalence could not be demonstrated for weight loss or changes in body composition.

Intermittent energy restriction may be superior to continuous energy restriction for weight reduction, although a sample population of more than 300 participants would be required to demonstrate superiority with 80% power.

Aims To compare the safety of intermittent fasting (IF) with that of continuous energy-restricted diets (CERD) in patients with T2DM and metabolic syndrome who were overweight or obese and assess their effects on glycemic control and weight loss. Materials and methods We searched MEDLINE (Ovid), Embase, and SINOMED databases up to September 13, 2020. The major outcome was glycemic control and secondary outcomes were change in weight, fasting insulin, and lipid profile. Results Of 84 retrieved studies, 5 met our inclusion criteria. Of these, four studies comprising 355 participants were included in the meta-analysis.

Based on changes in HbA1c (-0.06, 95% confidence interval [CI] -0.27 to 0.16) and fasting plasma glucose (-0.27, 95% CI -0.76 to 0.22), IF and CERD had similar effects on glycemic control. Moreover, IF had a better effect on weight loss (-1.70, 95% CI -3.28 to -0.11 kg). Patients in both groups experienced similar improvements in fasting insulin and lipid profile as well as similar hypoglycemic events.

Nine trials (n = 894) were included, involving time-restricted feeding (TRF), alternate-day fasting (ADF), and 5:2 fasting (whole-day fasting, WDF). Compared with CER, IF was associated with greater reductions in body weight (MD = -1.29 kg; 95% CI, -1.98 to -0.61), BMI (MD = -0.34 kg/m 2; 95% CI, -0.55 to -0.13), LDL-C (MD = -0.08 mmol/L; 95% CI, -0.15 to -0.01), and controlled attenuation parameter (CAP) (MD = -15.13 dB/m; 95% CI, -28.87 to -1.39). No significant between-group differences were observed for magnetic resonance imaging-proton density fat fraction (MRI-PDFF), liver stiffness, transaminases, glucose-related indices, total cholesterol, triglycerides, or HDL-C.

The studies published between 2019 and 2025, included 508 participants in the IF groups and 386 in the CER groups. All trials assessed hepatic steatosis using ultrasound or MRI-PDFF. Participants’ mean age ranged from 31 to 61 years, and median BMI ranged from 26 to 33 kg/m 2 . Both male and female participants were included. Diagnoses were primarily based on NAFLD, MAFLD, or MASLD criteria. Sample sizes ranged from 15 to 110, and intervention durations ranged from 8 to 52 weeks. Across the eligible intervention arms, six used TRF, one used ADF, and three used WDF.

Sensitivity analyses excluding one crossover trial (n = 32) and studies with sample sizes < 50 did not materially affect the overall direction or magnitude of the pooled estimates (Supplementary Table S8). However, after these exclusions, the between-group difference in CAP was no longer statistically significant (MD = -11.97; 95% CI, -31.08 to 7.14; k = 3; p = 0.22; I 2 = 56.5%).

The meta-analysis included 16 articles (20 trials) with a total of 1,511 participants. All studies had a low risk of bias for random sequence generation. The IER and CER intervention equally improved MetS risk factors WC (MD = -0.47, 95% CI [-1.19, 0.25]), TG (MD = -0.02 mmol/L, 95% CI [-0.11, 0.07]), FPG (MD = -0.02 mmol/L, 95% CI [-0.10, 0.05]) and BP (systolic blood pressure: MD = 0.93 mmHg, 95% CI [-2.74, 4.61]; diastolic blood pressure: MD =1.15 mmHg, 95% CI [-0.24, 2.55]), but HDL-c (MD = 0.03 mmol/L, 95% CI [0.01, 0.05]) was significant improved in IER when compared with CER. For second outcomes, BW (MD = -0.8 kg, 95% CI [-1.26, -0.33]), BF (MD = -0.75 kg, 95% CI [-1.73, -0.13]) and FFM (MD = -0.49 kg, 95% CI [-0.92, -0.05]) were also significant improved in IER, and not for other outcomes.

The following inclusion criteria based on the population, intervention, comparison, and outcome approach were used to select studies eligible for this systematic review and meta-analysis: 1) a population of apparently healthy individuals aged ≥18 y with a normal weight, overweight, or obese, 2) parallel or cross-over RCTs with IER protocols, i.e., TRE, ADF, or the 5:2 diet, as the intervention group, and 3) CER as the control group, and 4) outcome measures included anthropometrics [body weight, BMI, fat mass (FM), fat-free mass (FFM), and waist circumference (WC)], and parameters related to fasting lipids and lipoproteins [total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triacylglycerol (TG)], fasting glucose and insulin concentrations, HOMA-IR, and blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)]. Only studies in which body weight and ≥2 of these aforementioned outcome measures were reported were considered for inclusion in this systematic review.

In total, 2043 participants were included in the studies, ranging from N = 8 to N = 118 participants per study arm. The mean age of the participants varied from 27 to 68 y, and their mean BMI from 22 to 40 kg/m 2. Most studies included both men and women [[26], [27], [28], [29], [30], [31],[33], [34], [35], [36],38,39,42,[44], [45], [46], [47],49,50]. In 1 study, only men participated [43], and in 8 studies, only women [[23], [24], [25],32,37,40,41,48]. The intervention periods ranged from 2 to 52 wk. In 1 study, however, postintervention measurements were performed as soon as participants had lost ≥5% of their baseline body weight. The median intervention period had a duration of 59 d in the IER group and 73 d in the CER group [42].

The studies included a range of 16 to 332 participants (n = 1768). Intervention periods ranged from 2 to 26 weeks. Age of participants ranged from 23 ± 1 to 68 ± 2.7 years old. The body mass index (BMI) of the participants ranged between 21.7 ± 0.8 kg/m 2 and 39.5 ± 6.0. The selected studies included both females and males, although the majority were females. The studies included participants with a range of body weights, with most of these restricted to participants with overweight and obesity or only obesity, whereas five studies included normal weight participants. We identified 12 RCTs on ADF/MADF, 8 on the 5:2 diet, and 4 on TRE. Fourteen studies compared IF with CER, eight studies compared IF with an ad libitum diet, and two studies used both ad libitum and CER as comparator diets.

Conversely, important limitations should be considered. Firstly, the GRADE evaluation of the certainty of evidence was downgraded due to considerable heterogeneity and incoherence in the primary outcome of body weight among the various diet strategy comparisons. These downgrades are reflective of unexplained inconsistencies in the treatment effects (heterogeneity) and variations in the direct versus indirect estimates (incoherence). Certainty of evidence was also downgraded for imprecision based on 95% CIs crossing the prespecified minimal important differences for the outcomes of interest. Many randomised clinical trials had small sample sizes, which would have influenced the precision of the effect estimates. Similar downgrades were applied for several secondary cardiometabolic risk factors. Secondly, evidence of serious concern was considered for indirectness in several analyses, particularly among intermittent fasting strategy comparisons. Only three randomised clinical trials of direct assessment between intermittent fasting diets were available, thereby limiting generalisability and resulting in downgrades for indirectness.39 52 102

Taken together with the evidence of the present literature, a serious risk of bias was not indicated because more than 80% of studies were considered to have low risk of bias.

In total, 5 studies (17.2%) were classified as having a low RoB, whereas the other studies (82.8%) were classified as having some bias concerns. This was mainly because most of these studies did not report whether outcome assessors were aware of the intervention received by the participants. Furthermore, all studies involved energy-restricted diets, and hence, participants were aware of their assigned intervention arm.

Overall, risk-of-bias assessments showed moderate to high risk of bias in at least one attribute. Because the interventions involved diet, all participants were aware of their assigned eating pattern, leading to a potential for performance bias in all studies. Two other sources of bias were present in some studies included in these analyses: incomplete outcome data as a result of missing outcome measures related to dropouts (nine studies) and selective reporting of results (four studies).

The high heterogeneity I 2 > 70% between the studies used in this meta-analysis could be attributed to various reasons such as the differences in study population, study design and study duration. The effect size for duration was taken into account in the model, with no statistical relevance, although the short time frames of the studies ranging from a few weeks to a maximum of 26 weeks limits a conclusive interpretation.

The results of the risk of bias assessment for the included trials are shown in Supplementary Fig. 1. A high risk of bias existed in the randomization process (domain 1) and missing outcome data (domain 3). Overall, 25% of the included studies had a high risk of bias.

Risk of bias assessment was performed in all the included studies. The assessment revealed that none of the studies were at low risk of bias (high quality), 10 of the studies were at moderate risk of bias (moderate quality), and 11 of the studies were at high risk of bias (low quality).

A small subset of trials had a duration of three weeks, the minimum threshold, typically reporting modest weight reductions (eg, 0.5-2 kg), consistent with early phase feasibility studies. Conversely, only five trials extended to 52 weeks or more, limiting the feasibility of undertaking a robust analysis for very long term outcomes.

The included studies focused on short-term effects of the intervention (up to 12 months), limiting the applicability of the evidence in this review to inform decision-making for longer durations. It would be beneficial for future studies to extend follow-up periods beyond 12 months to build a stronger evidence base for the long-term effects.

We are moderately confident in the results for weight loss when comparing intermittent fasting with no treatment. However, our confidence is low to very low for our other points of interest because most included studies did not use the most robust methods, they included few people, and reported results that were inconclusive.

Intermittent fasting in adults (no recommendations) Why the committee did not make a recommendation Some evidence was identified on intermittent energy-restriction approaches such as alternate-day fasting and time-restricted eating. This showed improvement for a few outcomes, but for most outcomes it was not effective. The committee also noted the variation in approaches to intermittent energy restriction and that there were problems with the studies, such as not being able to differentiate between the intervention and control for some outcomes. So they did not make recommendations on these diets but made a recommendation for research on intermittent fasting in adults to encourage better quality trials.

1.16.3 Ensure that dietary approaches for adults to support overweight and obesity management keep the person's total energy intake below their energy expenditure (also called an energy deficit or calorie deficit). This could be done by lowering specific macronutrient content (for example, low-fat or low-carbohydrate diets) or using other methods to limit overall energy intake. [2025]

1.16.5 Ensure that any dietary approaches that maintain an energy deficit are offered with support (for example by an appropriately trained healthcare professional such as a Registered dietitian or registered nutritionist) and follow up to help people maintain any weight loss in the long term. [2025]

Any of the following (each with different goal targets and not all for weight loss): calorie-restricted dietary pattern emphasizing variable macronutrient distribution ranges; Mediterranean; vegetarian; Portfolio diet; low-glycemic index; DASH; Nordic; partial meal replacements; intermittent or continuous calorie restriction; pulses; vegetables and fruit, nuts, whole grains, dairy foods