Introduction
Obesity has escalated into a global health crisis, with projections estimating that over 1.53 billion adults will be affected by 2035. This alarming figure, published by the World Obesity Federation in the World Obesity Atlas 2024, indicates that more than half of the adult population is at risk of being overweight or obese. Obesity is strongly associated with chronic diseases, including cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Approximately 60% of patients with type 2 diabetes are overweight or obese, highlighting the role of obesity in promoting insulin resistance. Obesity also significantly elevates the risk of cardiovascular diseases through mechanisms such as inducing structural and functional changes in the heart, activating inflammatory processes, altering hemodynamics, and affecting adipokine levels, as noted in the Clinical Consensus Statement of the European Society of Cardiology (ESC).
In response to the escalating obesity crisis, various dietary approaches for weight loss have gained popularity. Intermittent fasting (IF) has emerged as a promising dietary intervention for weight management and metabolic improvement. IF is a dietary pattern that involves regular periods of restricted food intake, stimulating the body’s metabolic adaptive mechanisms through periods of zero or very low-calorie intake. This approach has garnered attention as an alternative to traditional continuous energy restriction (CER) for weight loss.
Understanding Intermittent Fasting
Intermittent fasting (IF) refers to regular periods with no or very limited caloric intake. Common IF regimens include Intermittent Energy Restriction (IER) and Time-Restricted Eating (TRE). IER involves a significant reduction in energy intake during specific fasting periods, with normal eating habits during non-fasting periods. This periodic adjustment induces the body to utilize stored fat as an energy source, potentially achieving weight control, improved metabolic health, and prevention of related diseases.
Types of Intermittent Fasting
- Alternate Day Fasting (ADF): This form of IER involves alternating "fasting days" and "feeding days." On feeding days, food can be consumed freely, while on fasting days, food intake is either completely restricted or significantly reduced.
- 5:2 Fasting (Twice-Weekly Fasting): Individuals control calorie intake on any two chosen days of the week, maintaining a normal diet without deliberately restricting food types on the remaining five days. The 5:2 model is often considered easier to adhere to long-term due to its allowance for normal eating most of the time.
- Time-Restricted Eating (TRE): Restricts eating to a specific window of time each day, such as an 8-hour window, with fasting for the remaining 16 hours.
Numerous studies have indicated that intermittent fasting can effectively reduce body weight and improve metabolic indicators such as blood glucose and blood lipids, with potential benefits for cardiovascular and metabolic health.
Conflicting Evidence and Knowledge Gaps
Despite the extensive research on IF for obesity, inconsistencies and gaps in the available evidence persist. Disagreements exist regarding the effectiveness of intermittent fasting in weight loss and metabolic marker improvement. For instance, one study found IF superior to CER in improving triglyceride (TG) levels, while another indicated that short-term IF may increase glycan TG levels, contradicting the common belief that IF improves metabolic markers.
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Furthermore, the effectiveness and safety of different intermittent fasting durations remain unclear. No conclusive evidence exists regarding which IF mode is the most effective and safe, adding complexity to research and creating confusion for clinicians and patients when choosing an IF regimen.
Meta-Analysis of Randomized Controlled Trials
To address these inconsistencies and gaps, a systematic review and meta-analysis was conducted to provide a comprehensive assessment of existing randomized controlled trials on IF in obese adults. This meta-analysis aimed to clarify the effects of IF on weight loss, metabolic markers, and cardiovascular health, while also exploring the differences between various IF modes. The ultimate goal was to provide clinicians and patients with the latest evidence and recommendations on IF for obese adults, guiding clinical practice and personal health management.
Methods
This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration ID: CRD420251036588).
Search Strategy
A comprehensive search was conducted in PubMed, Embase, and Web of Science, from their inception to March 2025. Keywords used included "Intermittent Fasting," "Intermittent Energy Restriction," "Time-Restricted Eating," "Alternate Day Fasting," "Twice-Weekly Fasting," "continuous energy restriction," "5:2 diet," "fasting-mimicking diet," "time-restricted feeding," and terms related to obesity. The search was restricted to English-language articles with human participants.
Study Selection
Initial records were exported to EndNote software for screening, and duplicates were excluded. The selection process was based on titles/abstracts, followed by full-text screening according to inclusion and exclusion criteria based on the PICOS standards (population, intervention, comparison, outcome, and study design).
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- Inclusion Criteria: Participants aged ≥ 18 years with a body mass index ≥ 25 kg/m², various forms of IF (IER, ADF, 5:2 or 4:3 diets, TRF, TRE), control groups maintaining daily eating habits, and primary outcomes including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Only randomized clinical trials or randomized controlled trials with parallel groups were included.
- Exclusion Criteria: Non-original research, animal studies, non-randomized trials, studies comparing IF with a CR group without overweight or obese participants, or studies using a Mediterranean diet as the comparison group.
Data Extraction
Data extraction was conducted by independent authors, with disagreements resolved through discussion. Extracted data included the first author, year of publication, study design, number of groups, participant characteristics (sample size, biological sex, age, BMI, health status), intervention characteristics (IF and CON dietary patterns, duration, protocols), and all outcome indicators.
Risk of Bias Assessment
The risk of bias in the included studies was assessed using the Cochrane Collaboration’s Risk of Bias Tool, focusing on random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
Meta-Analysis
Pooled standard mean differences (MD) and 95% confidence intervals were calculated. Heterogeneity was assessed using the I² statistic, with values < 25% indicating low heterogeneity, 25-75% indicating moderate heterogeneity, and > 75% indicating high heterogeneity. Publication bias was assessed using funnel plots. Sensitivity analysis was conducted by removing individual studies when there were nine or more trials reporting results for an outcome measure. Subgroup analyses were performed based on intervention duration and IF mode when seven or more trials reported results.
Results of the Meta-Analysis
The database search identified numerous studies, with a subset addressing weight loss in overweight and obese patients. These studies included small randomized controlled trials (level I evidence) and trials comparing weight after IF to baseline weight with no control group (level II evidence). The trials were often of short duration (2 to 26 weeks) with low enrolment (10 to 244 participants); two studies were of 1-year duration.
Weight Loss and Body Composition
All IF trials found weight loss ranging from 0.8% to 13.0% of baseline weight without serious adverse events. Twelve studies comparing IF to calorie restriction found equivalent results. The meta-analysis revealed that IF significantly reduced BW (MD: -3.73 kg, 95% CI: -5.29, -2.17) and BMI (MD: -1.04 kg/m², 95% CI: -1.39, -0.70) in overweight/obese adults.
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Lipid Profiles and Blood Pressure
IF effectively improved lipid profiles, including TC (MD: -6.31 mg/dl, 95% CI: -12.36, -0.26) and LDL (MD: -5.44 mg/dl, 95% CI: -12.36, -0.26). However, short-term IF (≤ 12 weeks) may have resulted in a temporary elevation of TG (MD: 13.22 mg/dl, 95% CI: 3.39, 23.05), whereas long-term intervention (> 12 weeks) optimized lipid metabolism benefits. In addition, IF significantly reduced DBP (MD: -3.30 mmHg, 95% CI: -5.47, -1.13) but had no significant effect on SBP, FPG, and HbA1c.
Subgroup Analyses
Subgroup analyses showed that alternate day fasting (ADF) was superior to time-restricted eating (TRE) in terms of weight loss and improvement in LDL.
Limitations
The study's limitations include the short intervention periods (≤ 12 weeks) and high heterogeneity of most studies. Standardized long-term trials are needed to validate the sustained benefits and safety of IF.
Intermittent Fasting vs. Calorie Restriction
Twelve studies compared IF to calorie-restricted diets and found equivalent weight loss in both groups. Study duration ranged from 8 weeks to 1 year, with a combined total of 1206 participants (527 undergoing IF, 572 using calorie restriction, and 107 control participants), demonstrating weight loss of 4.6% to 13.0%. Adherence appeared similar for both weight loss strategies. The largest study comparing IF with calorie restriction, by Headland et al in 2019, involved 244 obese adults who achieved a mean 4.97-kg weight loss over 52 weeks versus a mean weight loss of 6.65 kg with calorie-restricted diets (P = .24). All other comparisons of IF and calorie-restriction diets also found similar results between both groups. In several studies, those in the IF group consumed the same amount of calories or less than those in the calorie-restriction group.
Fat Loss and Weight Regain
Most of the weight loss with IF is fat loss. A 2011 study by Harvie et al calculated that 79% of weight loss was due to loss of fat specifically. Participants regained some weight during follow-up after intervention, although average body weight remained statistically significantly lower than baseline levels. Weight regain did occur after 6 months. In 6 comparisons of IF and calorie restriction, the amount of weight regained after IF and calorie restriction was similar.
Practical Considerations and Safety
The practical length of a fast to effect changes in weight appears to be 16 hours. In IF studies with a daily fasting intervention, participants were able to maintain a minimum daily fast of about 16 hours, with an 8-hour eating window each day. Combining exercise with IF improved weight loss in a 2013 study by Bhutani et al of 64 obese patients.
Special Populations
Eight Ramadan studies examined weight loss in obese adults (n = 856). Weight losses ranged from 0.1 kg to 1.8 kg. Five studies exclusively enrolled individuals with type 2 diabetes. Kahleova et al compared a daily fast of at least 16 hours to caloric restriction (n = 54). Both groups experienced decreases in insulin levels, but IF participants had significantly lower fasting glucose levels.
Safety Concerns
No serious adverse events were reported in the IF trials. Fasting-related safety concerns include mood-related side effects and binge eating, among other symptoms. Use of IF in patients with diabetes poses a risk of hypoglycemia.
Comparison with Other Weight Loss Methods
A systematic review of 40 studies found that intermittent fasting was effective for weight loss, with a typical loss of 7-11 pounds over 10 weeks. However, different study designs and methods of intermittent fasting were used, and participant characteristics differed. A randomized controlled trial that followed 100 obese individuals for one year did not find intermittent fasting to be more effective than daily calorie restriction. A one-year randomized trial also did not find intermittent fasting (16:8 method) more beneficial than calorie reduction without a restricted eating time.
The Johns Hopkins Study
The Johns Hopkins researchers randomly assigned 41 adults with obesity and prediabetes to either time-restricted eating (TRE) with a 10-hour eating window or a regular eating pattern for 12 weeks to compare weight loss and other measures of metabolic health. Both groups lost about the same amount of weight, and there were no real differences in fasting glucose, waist circumference, blood pressure, or lipid levels.
Harvard T.H. Chan School of Public Health Study
Researchers at Harvard T.H. Chan School of Public Health conducted a systematic review and network meta-analysis of clinical trials that compared how intermittent fasting diets, traditional calorie-restricted diets, and restriction-free diets impacted participants’ body weight and various measures of cardiometabolic health. The study, analyzing 99 clinical trials across more than 6,500 participants, found that for weight loss, intermittent fasting and traditional calorie-restricted diets were on par and were more effective than restriction-free diets.