Calorie Restriction With or Without Time-Restricted Eating in Weight Loss

Due to flaws in its design and size, this trial unfortunately provides little relevant evidence on the scientific question of interest. Three major limitations are relevant:

1. The recommended composition of the diet — a low-fat, high-carb diet, with no focus on food quality — is sorely outdated, based on science of the 1990s, for optimal weight loss. This is a severe handicap for interpretation.

2. The scientifically and clinically relevant and interesting question about intermittent fasting is about its potential impact on host and microbiome physiology, which might allow weight loss without calorie counting. However, the investigators controlled the recommended calories in both groups. This fails to address the fundamental question of interest.

3. The trial was much too small, limiting statistical power, and dropout was not handled correctly; in weight loss trials, patients who drop out should be included in the analysis as having no weight loss. This was not done, overestimating the actual weight loss in both groups.

In sum, this trial highlights the importance of setting up an appropriate study design from the start, to be able to advance science.

Weight loss is an important goal in the management of obesity. Calorie restriction (CR) promotes weight loss in obesity; however, other lifestyle interventions are needed, as CR is not a sustainable way to achieve long-term weight loss. Time-restricted eating (TRE) has been studied as a lifestyle intervention to promote weight loss and other metabolic benefits, as TRE aligns dietary intake with the body’s intrinsic circadian rhythms of metabolism. Whether TRE has advantages over CR for promoting weight loss and metabolic benefits in obesity is an active focus of clinical investigation. Liu and colleagues recently reported in The New England Journal of Medicine the results of a 12-month randomized controlled trial comparing CR with or without 8-hour TRE for weight loss in obesity. The primary outcome was the difference between groups in weight loss from baseline. The authors randomized 139 participants with obesity (mean age±SD, 31.9±9.1 years; ~50% women; BMI ~31 kg/m²) to CR (25% reduction in daily calorie intake from baseline) with or without TRE (reduction in the daily eating window from 10 to 8 hours) in a 1:1 ratio. Both groups received dietary counseling by trained health coaches, written booklets, health education sessions, and support in the form of telephone calls and app messages. Both groups adhered to their assigned intervention for approximately 85% of the study period.

Both groups experienced significant weight loss from baseline over 12 months, with mean weight change –8 kg in the CR+TRE group and –6.3 kg in the CR group. However, there was no significant difference in weight loss between groups (–1.8 kg; P = .11). Over 12 months, both groups experienced reductions in body fat mass, lean mass, abdominal visceral fat, subcutaneous fat, liver fat, and systolic and diastolic blood pressure; however, there were no significant between-group differences in these parameters. Both interventions were generally well-tolerated.

The results of this study suggest that both CR and CR+TRE are effective for weight loss in obesity in the context of a clinical trial involving significant support to participants over a 12-month period. While there was no significant statistical difference in weight loss between groups over 12 months, the results of this study do not exclude the possibility of benefits of TRE over CR. The trial participants had a fairly narrow baseline eating window (10 hours 23 minutes); therefore, reducing this by only about 2 hours to an 8-hour eating window may not have been a sufficient change from baseline to test TRE in combination with CR. The 95% confidence interval for the difference in weight loss between groups was –4 to +0.4 kg, suggesting that CR+TRE could promote as much as a 4-kg greater weight loss than CR alone. These were also relatively healthy, young participants (baseline HbA1c, ~5.3; hypertension, 16%–17%), which also limits the ability to detect meaningful effects of TRE on markers of cardiometabolic health. Thus, while the results of this study provide additional data on the effects of CR and TRE on weight loss in obesity, TRE remains an intervention that may provide a practical tool for promoting long-term weight loss, with the potential to provide greater cardiometabolic health benefits than CR alone; this will be addressed by future studies involving individuals with greater circadian rhythm disruption at baseline (eg, longer baseline eating windows) and concomitant cardiometabolic risk (eg, metabolic syndrome and type 2 diabetes mellitus).

Fasting practices have a long tradition of use in religious and ceremonial practices. More recently, these practices have gained popularity as alternative weight-loss methods, as many traditional methods only demonstrate modest benefits (<5% weight loss at 12 months).¹ Although fasting type diets have shown benefits in some populations in observational trials, there have not been long-term data, especially in comparison with traditional caloric-restricted diets. 

To help answer this question, researchers from China completed a 1-year trial in which 139 subjects with obesity (average weight, 88 kg; BMI, 31) were randomized to:

• Time-restricted eating (eating only between 8 AM and 4 PM) plus calorie restriction, or
• Daily calorie restriction alone

The calorie-restricted diet consisted of a regimen many clinicians are familiar with: 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women.

Endpoints:

• The primary endpoint was differences in body weight.
• Secondary endpoints were changes in waist circumference, BMI, body fat, and measures of metabolic risk factors.

Results

The dropout rate was 15% and lower than anticipated (20%) and adherence to the diets was good at >80% overall.

Weight loss was –8.0 kg (~9%) in the combined group versus –6.3 kg (~7%) in the calorie-restriction group. This 1.8 kg difference was less than the 2.5 kg difference on which the study was powered and was not statistically significant (P = .11). Notably, both groups outperformed the ≤5% weight loss that was observed in many long-term traditional diets. The 9% weight loss observed in the combined group is greater than the 2% to 4% weight loss that was observed in a review of time-restricted diets alone.²

Secondary measures were similarly not significantly different between groups.

Adverse events: Overall, mild, (fatigue and dizziness), and similar in both groups.

Conclusions

The authors concluded that an 8-hour time-restricted–eating regimen did not produce greater weight loss or secondary metabolic changes than the regimen of daily calorie restriction alone. Overall, they concluded that calorie restriction explained most of the beneficial effects seen with the time-restricted–eating regimen. However, they did point out that: “our findings suggest that the time-restricted–eating regimen worked as an alternative option for weight management. We speculate that these data support the importance of caloric intake restriction when adhering to a regimen of time-restricted eating.” Basically, the authors could not rule out that time-restricted eating did not help some members of the combined group achieve the intended weight loss.

Limitations

Findings cannot be generalized to:

• Patients with diabetes or cardiovascular disease
• Different periods and types of time-restricted eating
• Persons of other races or ethnic groups

Total energy expenditure was not assessed.

Physical activity was not controlled.

The biggest limitation may have been the participants enrolled.  As pointed out in the accompanying editorial by Drs. Laferrère and Panda³ the participants were at an average eating window of 10 hours and 23 minutes, which is already much better than the nearly 15 hours seen in some populations.⁴  The approximate 2-hour reduction may not be significant. In addition, the level of obesity and metabolic derangement was relatively minimal, which leaves little room for the potential benefit of a time-restricted diet in patients with metabolic disease. Overall, the authors conclude that “the applicability of this trial to wider populations is debatable.”

Bottom line: Caloric restriction is still the key message in helping our patients lose weight. 

Adding time restriction to calorie restriction may have benefits in subpopulations to attain weight loss goals; however, this was difficult to ascertain from this study. Continue to reserve time-restricted diets for patients whose eating pattern and metabolic status might provide the predictive value of adding this intervention to caloric restriction. 

References

1. Johnston BC, Kanters S, Bandayrel K, et al. Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults: a Meta-analysis. JAMA 2014;312(9):923-933. https://doi.org/10.1001/jama.2014.10397
2. Manoogian ENC, Chow LS, Taub PR, et al. Time-restricted Eating for the Prevention and Management of Metabolic Diseases. Endocr Rev. 2022;43(2):405-436. https://doi.org/10.1210/endrev/bnab027  
3. Laferrère B, Panda S. Calorie and Time Restriction in Weight Loss. N Engl J Med. 2022;386(16):1572-1573. https://doi.org/10.1056/nejme2202821
4. Gill S, Panda S. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans That Can Be Modulated for Health Benefits. Cell Metabolism. 2015;22(5):789-798.https://doi.org/10.1016/j.cmet.2015.09.005