CardioNerds Journal Club is a monthly forum for CardioNerds to discuss and breakdown recent publications on twitter and are produced with a corresponding infographic and detailed blog post. For more information, check out the CardioNerds Journal Club Page. This Journal Club focuses on the STELLAR Trial

Table of contents for the The Stellar Trial summary:

• Visual abstract
• Summary
• References
• Credits
• Twitter Archive

September 2023

Calorie Restriction with or without Time-Restricted Eating in Weight Loss

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., et al.

https://www.nejm.org/doi/full/10.1056/NEJMoa2114833

Relevant literature

Study Rationale

Identification of an alternative and feasible dietary intervention for weight loss.

Study Objectives

The study aims to assess whether time-restricted eating with calorie restriction as compared with daily calorie restriction alone for the effects on weight loss and metabolic risk factors in obese patients.

• Trial
  • Conducted in Guangzhou, China and was approved by the IRB at Nanfang Hospital of Southern Medical University.
  • Participants were recruited via promotional leaflets, information on the internet, and community screenings
• Intervention

1. Randomly assigned 1:1 to time-restricted eating regimen or daily-calorie restriction regimen for 12 months
   1. Interventions for both groups:
      1. Prescribed diet:
         1. 1500-1800kcal diet per day for men; 1200-1500kcal diet per day for women
         1. Combination of 40-55% of calories from carbohydrates, 15-20% from protein, 20-30% from fat
      1. All participants received dietary counseling by trained health coaches for duration of trial and information booklets with portion advice, sample menus and attended health-education sessions monthly
      1. Instructed to maintain usual daily physical activity throughout trial
      1. First 6 months:
         1. Required to write daily dietary log, photograph food, note time of meals on custom app
         1. Two researchers used this information to assess dietary intake
         1. Participants received follow-up telephone calls or app messages 2x/week and met with health coach every 2 weeks for adherence assessment and aid
         1. Received one protein shake per day
      1. Second 6 months:
         1. Maintain diet regimens
         1. Fill out lot with pictures and mealtimes 3 days per week
         1. Participants received follow-up telephone calls and app messages 1x/week and met with health coach monthly
   1. Time-restricted eating group:
      1. Instructed to consume prescribed calories from 8:00 am to 4:00 pm each day
      1. Only non-caloric beverages permitted outside 8hr period
   1. Daily-calorie restriction only group:
      1. Instructed to consume prescribed calories without time restriction
   1. Adherence based on number of days participant met requirements as above

Enrollment Criteria

1. Inclusion criteria: age 18-75, BMI 28-45
2. Exclusion criteria: acute or chronic viral hepatitis, malignant tumors, diabetes, serious liver dysfunction, chronic kidney disease, current smoking, serious cardiovascular or cerebrovascular disease within 6 months before randomization, severe GI disease or GI surgery within 12 months, active participation in a weight-loss program, use of medications that affect weight or energy balance, and current or planned pregnancy

Primary Outcome

• Primary Outcome: Difference between the two groups in the change from baseline in body weight at 12 months

Secondary Endpoints:

• Secondary Outcomes: Changes in waist circumference, body fat, body lean mass, and metabolic risk factors including levels of plasma glucose, insulin sensitivity, serum lipids, and blood pressure

Statistical Analysis

Intention to treat analysis. Data were presented as least-squares means with 95% confidence intervals for continuous variables. The 95% confidence intervals are not adjusted for multiple comparisons and should not be used to infer definitive treatment effects. A two-sided P value of less than 0.05 was considered to indicate statistical significance for the primary outcome.

Baseline Characteristics

• 139 patients were randomly assigned to time restricted eating (69) or daily calorie restriction (70). Of the total number, 135 completed 6 months of intervention and 118 completed the full 12 months of intervention.
• Baseline demographic and clinical characteristics were similar in both treatment groups.
• Mean age was 31.9 and the mean weight was 88.2kg
• Adherence: calculated as the mean percentage of days participants adhered to both the prescribed calories and eating period
  • 84.0 +/- 16.1% in the time-restricted eating group
  • 83.8 +/- 12.6% in the daily calorie restriction group

Outcomes

Primary Outcome

• The mean weight change from baseline to 12 months was –8.0 kg (95% CI –9.6 to –6.4) in the time-restricted eating group and –6.3 kg (CI –7.8 to –4.7) in the daily calorie restriction group.
• No significant difference between the two groups in weight change (net difference –1.8 kg, 95% CI –4.0 to 0.4; p=0.11)
• Subgroup analysis showed weight changes were similar for the two groups

• Waist circumference and BMI changes were similar between the two groups
• Body fat mass at 12 mo was reduced by 5.9 kg (95% CI –7.1 to –4.7) from baseline in time-restricted eating group and by 4.5 kg (95% CI, -5.6 to –3.3) in the daily calorie restriction group; no substantial differences in the two groups
• Body composition:
  • Both diets led to loss of lean mass, abdominal visceral fat, subcutaneous fat, and liver fat; no differences between the two groups
  • Both groups had similar measures of trunk fat and appendicular lean mass at 12 months
• Cardiometabolic risk factors:
  • Both groups associated with reduced systolic and diastolic blood pressures over 12 months, no substantial between-group differences
  • Fasting glucose levels, 2hr postprandial glucose levels, scores on insulin disposition index and HOMA-IR, and lipid levels were similar in the two groups

Adverse Events

• No deaths or serious adverse events were reported during the trial
• Occurrences of mild adverse events like fatigue, dizziness, headache, decreased appetite, upper abdominal pain, dyspepsia, and constipation were similar in the two groups

• The trial was designed to determine if time-restricted eating with caloric restriction as compared to daily caloric restriction alone resulted in a greater change from baseline in body weight. 
  • The study ultimately found there was no statistically significant difference in change from baseline body weight at 12 months when adhering to a time-restricted eating regimen as compared to daily calorie restriction.
  • Based on this, the authors conclude the weight loss documented in both groups is explained by the caloric restriction alone, and not the time-restriction.
• Limitations & Considerations
  • This study excluded patients with diabetes or cardiovascular disease, and thus cannot be generalized to these patient populations, many of which often struggle with obesity.
  • This study cannot be generalized to persons of other races or ethnic groups.
  • Total energy expenditure was not assessed during this trial.
  • Physical activity was not controlled in this trial in efforts to examine the effects of diet regimens on weight loss in isolation.

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. doi:10.1001/jama.2014.10397
2. Lowe DA, Wu N, Rohdin-Bibby L, et al. Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. JAMA Intern Med. 2020;180(11):1491–1499. doi:10.1001/jamainternmed.2020.4153

Summary by: Dr. Cali Clark @CaliRClark and Dr. Hamza Patel @Hamza_Patel123

Visual abstract by: Dr. Christian Andersen @CFAndersenMD

Trial Tweets by: Dr. Rachel Goodman @goodmra1

Moderator of Twitter during CardsJC by: Dr. Hamza Patel @Hamza_Patel123

Promo by: Dr. Rachel Goodman @goodmra1

Under the guidance of House Chief: Dr. Alaa Diab @DrAlaaDiab & Director of CardsJC Dr. Devesh Rai, @DeveshRaiMD

Supported by House Faculty: Dr. Dinu Balanescu @dinubalanescu, Dr. Ty Sweeney @TySweeney6, Dr. Saahil Jumkhawala @saahilaj, and Dr. Eunice Dugan @EuniceDuganMD Faculty experts: Dr. Martha Gulati @DrMarthaGulati, Dr. Alison Bailey @a_l_bailey, Dr. Seth Martin @SethShayMartin, Dr. Eugenia Gianos @EugeniaGianos