The latest longitudinal study on the subject was published on 21st April 2022 in The New England Journal of Medicine (NEJM). A randomized clinical trial was conducted to assess the impact of caloric restriction plus time-restricted eating on weight loss and metabolic risk factors in obese patients compared with daily caloric restriction alone. So far, we don’t know if time-restricted weight-loss diets are effective and safe over the long term.

Trial Design and Oversight

Researchers randomly assigned eligible trial participants in Guangzhou, China, to receive a time-restricted diet regimen or a daily caloric restriction regimen for 12 months. The observers (trial staff) were unaware of the assignments.

From November 30, 2018, to July 28, 2021, a total of 139 patients were randomly assigned to receive time-restricted eating (69 participants) or daily caloric restriction (70 participants). Among all randomized patients, 135 participants (97.1%) completed the 6-month intervention, and 118 (84.9%) completed the 12-month intervention (Table 1).

The participants’ mean (±SD) age was 31.9±9.1 years, and the mean weight was 88.2±11.6 kg. The baseline characteristics of participants in the two diet groups were similar, and they were typically obese (Table 1 and Table 2). In addition, physical activity was similar during the 12 months of this trial (Table 2).

A steering committee oversaw the trial. The Institutional Review Board approved the trial protocol of Southern Hospital of Southern Medical University. All participants provided written informed consent. The last author designed the trial, and the first and last authors wrote the first draft of this article. All authors participated in the revision of the manuscript to ensure the completeness and accuracy of the data and the fidelity of the trial to the protocol. All trial participants came from the public by distributing leaflets and posters, posting recruitment information online, and conducting community screening. Participants were eligible if they were 18 to 75 years old and had a body mass index (weight [kg] divided by height [m] squared) of 28 to 45. Exclusion criteria included:

• acute or chronic viral hepatitis,
• malignancy,
• diabetes mellitus,
• severe hepatic dysfunction or chronic kidney disease,
• current smoking,
• severe cardiovascular or cerebrovascular disease within six months before randomization,
• severe gastrointestinal disease or gastrointestinal surgery within the past month,
• actively participating in a weight loss program,
• using medications that affect weight or energy balance,
• and are currently or planning to become pregnant.

Intervention Program

During the 12 months of this trial, men were on a diet containing 1,500 to 1,800 kcal/d and women on a diet containing 1,200 to 1,500 kcal/d. Both diets consisted of 40 to 55 percent of calories from carbohydrates, 15 to 20 percent from protein, and 20 to 30 percent from fat. This regimen contained approximately 75 percent of the participants’ daily caloric intake at baseline. For the first six months, participants had a protein meal replacement shake (Nutriease [Zhejiang Nutriease], a convenient meal replacement food) to take daily to help improve their ability to tolerate calories and intake compliance. All participants received dietary counseling throughout the duration of the trial. Participants in the time-restricted diet group were asked to consume the prescribed calorie intake for 8 hours per day (8:00 a.m. to 4:00 p.m.). Outside of the 8-hour eating period, only non-caloric beverages are allowed. Participants in the daily calorie restriction group were allowed to consume the prescribed calorie intake for an unlimited time.

Trained health coaches conducted diet counseling. Participants received a written dietary information leaflet with some recommendations and sample menus (dietary calorie restrictions similar to that described in current dietary guidelines for macronutrient intake). Participants were encouraged to weigh food to ensure accurate reporting of caloric intake. During the first six months of the trial, all participants were asked to use a custom-built mobile research application (app) to record daily meals, take pictures of food consumed, and record eating time. Two researchers used each participant’s diaries and food photographs to assess participants’ meal timing and daily dietary intake based on nutrient content from the Chinese food composition table. Participants received follow-up phone calls or app messages twice a week and met with a health coach every two weeks to assess participant adherence to the program and help participants achieve their caloric goals for weight loss over the first six months. During the second 6-month trial, participants were asked to continue the dietary regimen and kept a weekly dietary diary with food photos and meal times for three days. During this time, patients received follow-up phone calls and app messages once a week and met with a health coach once a month. All participants participated in monthly health education sessions and maintained routine daily physical activity throughout the trial period.

Adherence to the dietary plan was determined based on the number of days participants met the assigned dietary requirements. Participants in the daily calorie restriction group were instructed to limit their food intake and follow a prescribed daily caloric intake goal; patients in the time-restricted diet group were instructed to eat within the prescribed daily eating period and adhere to the daily caloric intake goal.

Statistical analysis

Assuming an expected dropout rate of 20%, it was estimated that the inclusion of 138 participants (69 in each group) would provide the trial with 90% power, using a two-tailed test, at a significance level of 0.025, in the time-restricted diet group A significant difference of 2.5 kg (±2.4) in body weight was detected between the calorie restriction group and the daily calorie restriction group. Differences between the groups and standard deviations in weight loss were determined by comparing preliminary data obtained with a time-restricted diet plus caloric restriction regimen versus an unrestricted caloric restriction regimen.

Data analysis was performed according to the intention-to-treat principle. Point estimates were obtained, and standard efficacy errors and tested differences between treatment groups using the PROC MIXED procedure in SAS statistical software version 9.4 (SAS Institute). Group differences in trial outcomes were assessed using generalized linear models (for continuous variables) and chi-square tests (for categorical variables). In addition, repeated-measures correlations were adjusted using mixed-effects models and autoregressive correlation matrices to assess the effect of each dietary plan on changes in trial outcomes. Subgroup analyses were performed according to gender, BMI, insulin sensitivity, and adherence to the diet. Continuous variable data are presented as least squares means and 95% CIs. The 95% CIs were not adjusted for multiple comparisons and should not be used to infer definitive efficacy. A two-sided P value of less than 0.05 was considered statistically significant for the primary outcome.

Results

118 (84.9%) of the 139 participants who were randomly assigned completed 12 months of follow-up. Based on the 12-month changes in body weight from baseline, the time-restricted diet group lost 8.0 kg (95% confidence interval [CI], -9.6 to -6.4), and the daily calorie restriction group lost 6.3 kg (95% confidence interval [CI], -9.6 to -6.4), respectively CI, -7.8 to -4.7.). In terms of weight change, there was no statistically significant difference between the two groups (net difference -1.8 kg; 95% CI, -4.0 to 0.4; P=0.11). Consistent with the primary outcome were results for waist circumference, BMI, body fat, lean body mass, blood pressure, and metabolic risk factors. Furthermore, the number of adverse events did not differ significantly between the two groups.

Conclusion

Among obese patients, time-restricted diets did not produce more significant weight loss, body fat reduction, or reduction in metabolic risk factors than daily caloric restriction diets (National Key Research and Development Project of China [No. 2018YFA0800404]).

Obesity is a major global public health challenge. But, as of now, two things are certain:

1. It has been shown that weight loss through lifestyle changes is one of the most effective ways to lose weight.
2. The primary weight loss strategy for obese patients is daily caloric restriction.

However, most dietary weight-loss trials show modest weight loss (*5%) after 12 months, and long-term weight loss remains challenging. Therefore, identifying feasible and alternative dietary interventions is a priority in public health.

The original research paper can be found at this link.

To watch the short video reshared on our Instagram account (created by NEJM) please click here.

Reference

Deying Liu, M.D., Yan Huang, M.S., Chensihan Huang, M.D., Shunyu Yang, M.D., Xueyun Wei, M.D., Peizhen Zhang, M.D., Dan Guo, M.D., Jiayang Lin, M.D., Bingyan Xu, M.D., Changwei Li, Ph. D., Hua He, Ph.D., Jiang He, M.D., Ph.D., Shiqun Liu, M.D., Linna Shi, M.D., Yaoming Xue, M.D., and Huijie Zhang, M.D., Ph.D. Department of Endocrinology and Metabolism (D.L., Y.H., C.H., X.W., P.Z., D.G., J.L., B.X., S.L., Y.X., H.Z.) and the Department of Nutrition (S.Y., L.S.), Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans (C.L., H.H., J.H.). ”Calorie Restriction with or without Time-Restricted Eating in Weight Loss”, April 21. (2022), N Engl J Med 386:1495-1504 DOI: 10.1056/NEJMoa2114833 1838