Intermittent Fasting and Obesity-Related Health Outcomes

Edward L. Giovannucci,Viji Chandran,Tuan Pham,Krista A. Varady,Sajesh K. Veettil,Kiera Roubal,Chanthawat Patikorn,Nathorn Chaiyakunapruk,Yeong Yeh Lee

doi:10.1001/jamanetworkopen.2021.39558

Abstract

Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.

Highlights

Intermittent fasting (IF) has recently gained much public interest as a weight loss approach.1 IF is a unique dietary strategy defined as periods of eating alternated with periods of not eating.2 IF focuses on when food is consumed and total quantity consumed
The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity
Meaning This review suggests that intermittent fasting may have a beneficial role in improving anthropometric and cardiometabolic outcomes, especially for adults with overweight or obesity

Summary

Introduction

Intermittent fasting (IF) has recently gained much public interest as a weight loss approach. IF is a unique dietary strategy defined as periods of eating alternated with periods of not eating (fasting). IF focuses on when food is consumed and total quantity consumed. Intermittent fasting (IF) has recently gained much public interest as a weight loss approach.. IF is a unique dietary strategy defined as periods of eating alternated with periods of not eating (fasting).. IF focuses on when food is consumed and total quantity consumed. IF works through an altered liver metabolism, referred to as the metabolic switch, where the body periodically switches from liverderived glucose to adipose cell–derived ketones during fasting periods. Fasting stimulates adaptive cellular responses including improved glucose regulation, increased stress resistance, suppressed inflammation, and the upregulation of autophagy where damaged molecules are removed or repaired to defend against oxidative and metabolic stress.. It is hypothesized that altering body metabolism will lead to long-term health benefits. Fasting stimulates adaptive cellular responses including improved glucose regulation, increased stress resistance, suppressed inflammation, and the upregulation of autophagy where damaged molecules are removed or repaired to defend against oxidative and metabolic stress. It is hypothesized that altering body metabolism will lead to long-term health benefits.

Methods

Results

Discussion

Conclusion