Intermittent Fasting Trial Rumbles Weight-Loss Landscape
Adding a fasting period to cutting calories didn’t improve results, but experts say the popular approach warrants more study.
Intermittent fasting as a means of losing weight has soared in popularity in recent years, but without definitive trials supporting the approach. Now a new small, randomized trial may only serve to muddy the waters, with experts saying it fails to offer conclusive answers about time-restricted eating as a way to lose weight.
The study, led by Deying Liu, MD (Nanfang Hospital, Southern Medical University, Guangzhou, China), showed that people with obesity who reduced their daily calorie intake by 25% did not boost weight loss by also adhering to an intermittent-fasting regimen that confined eating to an 8-hour window each day.
Mean weight loss at 1 year was 8.0 kg (17.6 lbs) among those who restricted when they ate and 6.3 kg (13.9 lbs) among those who ate throughout the day, a nonsignificant difference (P = 0.11). The proportions of participants who had a weight loss of more than 5%, 10%, or 15% didn’t differ between groups, the researchers report in the April 21, 2022, issue of the New England Journal of Medicine.
Moreover, intermittent fasting did not provide any benefits in terms of other measures of body composition and cardiometabolic risk.
“Our data suggest that caloric intake restriction explained most of the beneficial effects of a time-restricted eating regimen,” the authors write. “However, our results support a strategy of time-restricted eating combined with caloric intake restriction (prescribed according to current dietary guidelines) as a viable and sustainable approach for obesity management.”
But Dariush Mozaffarian, MD, DrPH (Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA), told TCTMD the trial is not useful for addressing the viability of intermittent fasting for weight loss, pointing to three main deficiencies. First, the recommended composition of the diets consumed in both groups—low fat and high carbohydrates—runs counter to research over the past 20 years showing that higher-fat, low-carbohydrate diets are better, he said. Second, the main analysis focused only on the 85% of participants who completed the study, rather than assuming those who dropped out didn’t lose any weight, which is the standard approach. That overestimates the weight loss in the study, Mozaffarian said.
And finally, he said, the trial didn’t address the primary question of interest in this area—whether intermittent fasting alone (without cutting calories) results in more weight loss than caloric restriction alone. “The whole point of intermittent fasting is instead of caloric restriction you fast and then you eat as you wish the rest of the time,” he said, adding that one wouldn’t expect to see a difference in weight loss if calories are controlled in both groups, as was done here.
“I think it was not an informative study,” Mozaffarian stated.
A Dearth of Evidence
Some pilot studies, the authors note, have suggested that intermittent fasting leads to loss of body weight and fat mass in people with obesity, although one prior trial showed similar amounts of weight loss when comparing time-restricted but ad libitum eating with three structured meals per day.
“However, these studies did not provide information that was sufficiently conclusive to support evidence-based clinical guidelines for obesity,” Liu et al write. “In addition, the long-term efficacy and safety of time-restricted eating as a weight-loss strategy are still uncertain, and the long-term effects on weight loss of time-restricted eating as compared with daily calorie restriction alone have not been fully explored.”
For the current trial, investigators enrolled 139 individuals (mean age 32 years; 51% men) with obesity (body mass index [BMI] 28 to 45 kg/m2) living in Guangzhou, China, and randomized them to time-restricted eating (between 8 AM and 4 PM only, with noncaloric beverages allowed outside of that window) plus caloric restriction or to caloric restriction alone.
Participants in both groups were told to eat 1,500 to 1,800 kcal per day for men and 1,200 to 1,500 kcal per day for women, which represented a roughly 25% deficit compared with their normal consumption. In terms of diet composition, participants aimed to get 40% to 55% of their calories from carbohydrates, 20% to 30% from fat, and 15% to 20% from protein. All received one protein shake per day for the first 6 months, as well as dietary counseling for the duration of the study.
The study lasted 1 year, and during that time, the average proportion of days during which participants adhered to the prescribed calories and/or eating period was 84% in both arms. Average caloric deficit and intake from fats, carbohydrates, and protein were similar in the two groups.
Mean body weight at baseline was 88.2 kg (194.4 lbs), and that dropped during the study, with no significant difference between groups. Moreover, adhering to an intermittent-fasting regimen did not provide additional benefits in terms of changes in additional measures of adiposity and cardiometabolic risk or quality of life. There were no deaths or serious adverse events during the trial.
The Need for Better Studies
The potential benefits of intermittent fasting are less about adherence, Mozaffarian said, and more about potential biological changes induced by eating during a restricted time window. Fasting creates periods of potential ketogenesis and might alter adipocyte metabolism, liver metabolism, brain metabolism, and the microbiome in ways that possibly have benefits for long-term weight loss, he explained.
“Weight loss is not about just adherence. Weight loss is about biology. The types of foods you eat and perhaps when you eat them changes biology in different ways,” he said.
Also commenting for TCTMD, Sai Das, PhD (Jean Mayer USDA Human Nutrition Research Center on Aging and Friedman School of Nutrition Science and Policy, Tufts University), noted that the concept of time-restricted eating, or intermittent fasting, grew out of a desire to find an easier and less-burdensome approach to lowering the amount of calories consumed.
And although this trial failed to demonstrate an advantage for intermittent fasting in the context of daily caloric restriction, the message should not be that there is no benefit, Das said, pointing to “a very consistent pattern” of slightly greater weight and fat loss, as well as metabolic benefits, in that group. The trial, she said, suffered from inadequate statistical power, and the potential impact of intermittent fasting should be explored further.
Das highlighted a couple of other shortcomings of this trial. For one, the 8-hour restricted-eating window used in this study has not been shown to be feasible in other countries, including the United States, where the average eating window normally is 12 to 14 hours. In addition, she said she would have liked to have seen a 20% to 25% calorie deficit tailored to each participant, rather than use of general intake ranges for men and women overall. And finally, loss of lean mass was relatively high, accounting for about 30% of weight loss in each group. “I think it’s important that the type of calorie restriction that is implemented or prescribed . . . minimizes lean loss because over the long term that’s not going to be an optimal way to have any kind of weight change,” she said.
In an accompanying editorial, Blandine Laferrère, MD, PhD (Columbia University Irving Medical Center, New York, NY), and Satchidananda Panda, PhD (Salk Institute for Biological Studies, La Jolla, CA), also detail some of the limitations of the current analysis, and indicate that further research is warranted.
“The concept of time-restricted eating is evolving. Future studies will determine the appropriate duration of the time window for eating, who is most likely to benefit from this approach, how to implement time-restricted eating and the potential mechanisms for doing so, and the effects of time-restricted eating early in the day as compared with late in the day,” they write. “From a public health point of view, time-restricted eating may turn out to be an approach to accomplish calorie restriction and improve metabolic health without the resource-intensive approach of intentional calorie restriction.”
Asked why it’s so difficult to get definitive answers into optimal eating patterns from clinical trials, Mozaffarian pointed to a lack of funding for these types of studies. His group has issued a call to strengthen national nutrition research, advocating in 2020 for the creation of a new National Institute of Nutrition within the National Institutes of Health (NIH) and for a return of the Office of Nutrition Research in the NIH Office of the Director. The latter came to fruition last year, but, Mozaffarian said, “until we have a National Institute of Nutrition, I think we’re going to continue to have small, underfunded, equivocal science.”
Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …Read Full Bio
Liu D, Huang Y, Huang C, et al. Calorie restriction with or without time-restricted eating in weight loss. N Engl J Med. 2022;386:1495-1504.
Laferrère B, Panda S. Calorie and time restriction in weight loss. N Engl J Med. 2022;386:1572-1573.
- The study was supported by grants from the National Key Research and Development Project, the Outstanding Youths Development Scheme of Nanfang Hospital, the Key-Area Clinical Research Program of Southern Medical University, the Key-Area Research and Development Program of Guangdong Province, and the National Natural Science Foundation of China.
- Liu reports no relevant conflicts of interest.