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Evidence review: Intermittent fasting for weight loss and lower cardiometabolic risk

A US meta-analysis of clinical trials shows moderate- to high-quality evidence that intermittent fasting delivers weight loss, as well as improving markers for heart health and the prevention of type 2 diabetes, reports MedicalBrief. However, only alternate-day fasting and the 5:2 diet resulted in clinically significant weight loss of more than 5%.

Intermittent fasting is an umbrella term for several diets that alternate between feasts and fasts. The 5:2 diet involves eating normally five days of the week and restricting your calories on the other two days. Alternate-day fasting (ADF) calls for a fast day-feast day-fast day pattern; Time-restricted eating (TRE) refers to eating only during specific time windows each day.

The study was published in JAMA Network Open.

For the review, the researchers analysed 11 studies that comprised 130 trials of various intermittent fasting regimens. When the investigators looked at all of the studies as a whole, intermittent fasting did produce weight loss and improvements in risk factors for heart health. However, only alternate-day fasting and the 5:2 diet resulted in a clinically significant weight loss of more than 5%, the study showed.

“Our study demonstrates that the different forms of intermittent fasting, i.e., alternate-day fasting, the 5:2 diet and time-restricted feeding, are all effective weight loss interventions for people with obesity,” said study author Krista Varady, director of the Human Nutrition Research Unit at the University of Illinois, in Chicago.

“Intermittent fasting may be an effective means of lowering heart disease risk by decreasing blood pressure, low-density lipoprotein [LDL] or ‘bad’ cholesterol, and triglycerides,” she said. What’s more, these diets may help prevent type 2 diabetes by lowering insulin resistance and fasting insulin levels.

IF as a weight loss approach was found to be mostly successful in the initial phase (ie, 1-6 months), after which participants would frequently experience a plateau as additional weight loss was not further achieved because of the metabolic adaptation of the human body or decreased adherence to the assigned weight loss strategy, the authors note.

A report in MedicalXpress said Varady attributes most of these benefits as probably stemming from weight loss.

“All of these regimens induce a calorie restriction of 15% to 30% daily, which results in weight loss,” she said. “When an obese person loses weight, they almost always see reductions in LDL cholesterol, triglycerides, blood pressure and insulin resistance.”

One expert not involved with the study agreed that it’s too early to make any blanket recommendations.

“The study provides strong evidence that some, but not all, of the regimens result in weight loss and related decreases in body mass metrics and improvements in cardiometabolic risk factors, such as cholesterol levels, blood pressure and measures of insulin resistance,” said Benjamin Horne, director of cardiovascular and genetic epidemiology at the Intermountain Heart Institute in Salt Lake City, Utah.

The methods in this study that showed the most profound benefits tend to be the most difficult to follow, he noted. “Future studies should evaluate the ability of the average person to adhere to these regimens, because it is unclear that they are sustainable over the long term.”

The study also could not address if intermittent fasting reduces heart attacks or strokes or extends longevity. “It is unknown whether the average person can adhere to any of the four intermittent fasting regimens for a long enough period of time [years or decades] to affect those outcomes,” Horne added.

And importantly, he asked, can weight loss can be sustained without continuing the regimen?

There are also safety considerations. "The hype surrounding intermittent fasting may be leading to harms to unsuspecting people who want to achieve better health," Horne explained, "especially people with diagnosed chronic diseases and asymptomatic health conditions."

New York City dietician Robin Foroutan isn't a fan of the difficult-to-stick-with IF regimens that showed the greatest benefits in this study. “I only recommend time-restricted eating and fasting-mimicking diets,” said Foroutan. Fasting-mimicking diets work by tricking your body into thinking that you're fasting even though you're still eating. These methods are easier to follow so people are more likely to stay the course.

Study details

Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials

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

Published in JAMA Network on 17 December 2021

Key Points

Question What is the association of intermittent fasting with health outcomes and what is the strength of evidence of studies on intermittent fasting?

Findings This umbrella review of 11 meta-analyses of randomized clinical trials describing 104 outcomes associated with intermittent fasting on obesity-related health outcomes found 6 statistically significant associations of intermittent fasting supported by moderate to high quality of evidence. Outcomes associated with modified alternate-day fasting included a moderate reduction of body weight, body mass index, and cardiometabolic risk factors in 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.


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.

Evidence Review
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.

Conclusions and Relevance
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.


MedicalXpress article – Big review confirms power of fasting diets for weight loss (Open access)


JAMA Network Open article – Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials (Open access)


See more from MedicalBrief archives:


Fasting as a weight-loss intervention in gestational diabetes – Australian trial


Intermittent fasting: From Pythagoras to Fung


NHS scepticism over study claiming heart benefits of fasting diet


The pros and cons of intermittent fasting to lose weight



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