JAMA Review Details Current Evidence Base Surrounding Intermittent Fasting for Weight Loss

Nathorn Chaiyakunapruk, PharmD, PhD

Data from an umbrella review of evidence from randomized clinical trials examining intermittent fasting for weight loss is providing a comprehensive overview of the impact of the approach on numerous outcomes, including BMI, fat mass, cholesterol, glucose, and insulin resistance, among patients with overweight or obesity.

An umbrella review of meta-analyses of trials, data from the review, which was published in JAMA Network Open, provides evidence supporting the role of intermittent fasting, particularly alternate-day fasting, as an approach for weight loss in adults with overweight or obesity.

“Our review generated several key messages that should be highly relevant to clinicians and patients, especially those who have interest in adopting the practice of intermittent fasting,” wrote investigators.

With the quality of evidence from trials and studies examining dietary strategies for weight loss, a team led by Nathorn Chaiyakunapruk, PharmD, PhD, of the University of Utah College of Pharmacy, designed the current study with the intent of evaluating associations of intermittent fasting with health outcomes and the strength of evidence from randomized clinical trials. Through a search of the PubMed, Embase, and Cochrane database, investigators performed a search hoping to identify all meta-analyses of clinical trials published from inception through January 12, 2021.

Investigators identified a total of 11 meta-analyses comprising 130 randomized clinical trials for inclusion in their review. These trials had a median sample size of trials per meta-analysis was 38 (IQR, 24-69), median follow-up period of 3 (IQR, 2-5) months, and described 104 unique associations between different types of intermittent fasting with obesity-related health outcomes, with a median of 4 (IQR, 3-5) studies per association. Investigators noted none of the meta-analyses received a grade of high in regard to quality when assessed using AMSTAR-2, with 7 graded as moderate confidence and 4 as low confidence.

Of the 104 unique associations identified, 40% examined anthropometric measures, 33% examined lipid profile outcomes, 14% examined glycemic profile outcomes, and 1 examined associated with C-reactive protein, adiponectin, leptin, and ghrelin levels apiece. Effect sizes were recalculated using a random-effects model and quality of evidence per association was performed through application of GRADE criteria.

Types of intermittent fasting examined in the review were zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating. Zero-calorie alternate day fasting was defined as alternating days of fasting with zero caloric intake and days of ad libitum eating and modified alternate-day fasting was defined as alternating days of ad libitum eating and days of fasting with a total caloric intake of 0-40% per day for 3-5 days per week.

Overall, 28 statistically significant associations were observed for intermittent fasting with beneficial outcomes, including 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. Intermittent fasting was also found to be associated with reduced fat-free mass.

Investigators pointed out a single association supported by high -quality evidence was modified alternate-day fasting for 1-2 months, which was associated with a moderate reduction in BMI among healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease when compared with a regular diet. Additionally, 6 associations were supported by moderate quality and the remaining associations found to be significant were supported by very low (n=75) to low (n=22) low quality evidence.

“Our results support the role of intermittent fasting, especially modified alternate-day fasting, in adults with overweight or obesity as a weight loss approach with metabolic benefits. 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,” wrote investigators.

This study, “Intermittent Fasting and Obesity-Related Health Outcomes An Umbrella Review of Meta-analyses of Randomized Clinical Trials,” was published in JAMA Network Open.