Intermittent Fasting and PLEASE Don’t Just Read the Abstract

Background: There are many lifestyle modification strategies available as a way to aid in weight management.  Two in particular include calorie restriction and intermittent fasting. Caloric restriction is self-explanatory, however personal experience has been it can be difficult to maintain for long durations of time.  Intermittent fasting is a regimen that entails a shortened period of time for eating within a 24-hour period.  It is simple to follow which may make it easier to sustain for longer periods of time.

Paper: Liu D et al. Calorie Restriction with or without Time-Restricted Eating in Weight Loss. NEJM 2022. PMID: 35443107

Clinical Question: Does a time restricted + calorie restriction diet reduce body weight at 12 months when compared to a calorie restriction diet alone?

What They Did:

  • Randomized patients with obesity to:
    • Time Restriction + Calorie Restriction: Time-restricted eating (eating only between 8am and 4:00pm) with calorie restriction
    • Calorie Restriction Alone: Daily calorie restriction alone
  • For 12 months participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women
  • Both diets included a combination of:
    • 40 to 55% from carbohydrates
    • 15 to 20% from protein
    • 20 to 30% from fat
  • All participants were provided one protein shake per day for the first 6 months to help improve adherence to the permitted calorie intake
  • All participants received dietary counseling for the duration of the trial


  • Primary: Difference between the two groups in the change from baseline body weight at 12 months
  • Secondary:
    • Changes in waist circumference
    • Changes in body-mass index (BMI)
    • Changes in the amount of body fat
    • Changes in measures of metabolic risk factors


  • Recruited trial participants from the general public by distributing promotional leaflets and posters, posting recruitment information on the internet, and conducting community screenings
  • 18 to 75 years of age
  • Body-mass index between 28 and 45kg/m2


  • 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 gastrointestinal diseases or gastrointestinal surgery in the 12 months prior to randomization
  • Active participation in a weight-loss program
  • Use of medications that affect weight or energy balance
  • Current or planned pregnancy


  • 139 participants underwent randomization
    • 118 (84.9%) completed the 12-month follow up visit
  • Mean Weight Loss from Baseline at 12 Months
    • Time Restriction + Calorie Restriction: -8.0kg (95% CI -9.6 to -6.4)
    • Calorie Restriction Alone: -6.3kg (95% CI -7.8 to -4.7)
    • Net Difference: -1.8kg; 95% CI 04.0 to 0.4; p = 0.11
  • Results of waist circumference, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome.
  • No substantial differences between groups in adverse events 


  • Observers (trial personnel) were unaware of group assignments
  • Groups were evenly balanced at baseline in terms of male sex, age, body weight, body mass index, body fat mass and waist circumference
  • Adherence to the 12-month intervention was essentially the same between groups
  • Over 80% of participants adhered to their randomized intervention at 12 months, showing sustainability of both options


  • Trial performed in China, where diets and lifestyles may be different from those in the US or other countries
  • Excluded patients with diabetes and cardiovascular disease
  • Tested only one time period for intermittent fasting
  • Physical activity was not controlled for in this trial.
  • Selection bias based on how patients were recruited (i.e. advertisements)
  • Recall bias as patients may not accurately show their intake
  • Blinding easily compromised since patients obviously know what they did (Less of an issue since the outcome measure was simple and objective)


  • Assuming an anticipated dropout rate of 20% the authors estimated that an enrollment of 138 participants would provide the trial with greater than 90% statistical power to detect a significant difference of 2.5kg in body weight (+/-2.4) between the time restricted eating group and the daily calorie restriction group
  • Why did this trial fail to show a benefit with intermittent fasting:
    • When looking at the daily eating window, there was no difference between groups (≈10hr 20min).Essentially, this was a trial comparing intermittent fasting to intermittent fasting
    • Reviewing the supplement however there does appear to be a small difference between groups in terms of eating window
      • At 6 months: 8hrs vs 11hrs
      • At 12 months: 8hrs vs 11hrs
      • It is unclear to me which numbers are the real numbers, but regardless is an eating window that is 3hrs less really that meaningful?
    • The median physical activity per week was more in the caloric restriction group (15.0 vs 12.0) which would favor the caloric restriction group over a 1-year timeline. Additionally physical activity was not controlled for in this trial and could affect the ultimate outcomes

Author Conclusion: “Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction.” 

Clinical Take Home Point: Reading this paper has reminded me that the devil is always in the details and not the bottom line of the abstract.  When your daily eating window between groups is essentially the same you are not comparing calorie restriction with time restriction plus calorie restriction. This trial showed no difference between groups because there was no intervention difference between groups (i.e. the eating windows were essentially the same).


  1. Liu D et al. Calorie Restriction with or without Time-Restricted Eating in Weight Loss. NEJM 2022. PMID: 35443107

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "Intermittent Fasting and PLEASE Don’t Just Read the Abstract", REBEL EM blog, May 12, 2022. Available at:

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