Importance Several meta-analyses of randomized clinical trials have demonstrated the many health benefits of intermittent fasting.
Objective To grade the evidence from published meta-analyses of randomized clinical trials 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.
Evidence Review PubMed, Em base, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Meta-analyses of randomized clinical trials investigating effects of intermittent fasting in adults were included. The effect sizes of intermittent fasting were recalculated using a random-effects model.
In this umbrella review, we found beneficial associations of IF with anthropometric and cardio metabolic 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.
Intermittent fasting (IF) has recently gained much public interest as a weight loss approach. Intermittent fasting is a unique dietary strategy defined as periods of eating alternated with periods of not eating (fasting). Intermittent fasting 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 liver-derived 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 up regulation 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.
Clinical trials have demonstrated the benefits of IF for many health conditions, especially obesity, diabetes, and cardiovascular diseases, through reduced weight and improved cardio metabolic parameters. Several systematic reviews and meta-analyses of randomized clinical trials have been published and demonstrated several health benefits of IF as well. This umbrella review aimed to systematically identify relevant meta-analyses of randomized clinical trials of IF, summarize their findings, and assess the strength of evidence to provide an aggregate picture of benefits associated with each type of IF on obesity-related health outcomes.
The protocol of this study was registered with Open Science Framework (OSF) (Appendix in the Supplement). This umbrella review reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISM A) reporting guideline.
We performed sensitivity analyses by excluding primary studies having a high risk of bias rated by the Cochrane risk-of-bias tool for randomized clinical trials and excluding small-size studies (<25th percentile) from the identified associations.
Eleven meta-analyses were included (Figure) (justification for excluded full-text articles available in Table 2 in the Supplement). Eligible meta-analyses included 130 randomized clinical trials (45 unique randomized clinical trials) with a median (IQR) sample size per randomized clinical trials of 38 (24-69) studies and a follow-up period of 3 (2-5) months (Table 1). The quality of meta-analyses assessed using AMSTAR-2 found that none were rated as high confidence, 7 (64%) as moderate confidence, and 4 (36%) as low confidence.
Excluding randomized clinical trials with small size, associations initially graded as high or moderate quality retained the same rank (Table 5 in the Supplement). When removing randomized clinical trials with a high risk of bias (measuring 7 outcomes) with very low to low quality evidence, the strength of evidence of 2 associations was upgraded to moderate. These associations were (1) the use of M ADF for 1 to 3 months and the reduction of body weight in overweight adults compared with regular diet, continuous energy restriction, or TRE (MD, −2.55 kg; 95% CI, −4.43 to −0.68), and (2) the use of M ADF for 3 to 12 months and reduction of LDL-C in adults compared with regular diet and exercise (MD, −3.33 mg/DL; 95% CI)
To our knowledge, this study is the first umbrella review that systematically assessed the potential obesity-related health outcomes associated with different types of IF across a large spectrum of published meta-analyses of randomized clinical trials and evaluated the evidence by using well-recognized GRADE.
Several limitations of our study deserve discussion. Most randomized clinical trial included in our analysis were limited to short durations of follow-up (a median duration of 3 months) and relatively small number of sample size (median 38 participants).
This umbrella review found beneficial associations of IF with anthropometric and cardio metabolic outcomes that were supported by moderate to high quality of evidence. Our results support the role of IF, especially M ADF, in adults with overweight or obesity as a weight loss approach with metabolic benefits.
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