Restricting calories drives impact of intermittent fasting on weight loss, but more research needed

22 Apr 2024 --- Researchers suggest restricting calories is more important for weight loss than meal timing, finding no benefits for a time-restricted eating pattern over a usual one when calorie intake was constant. Experts support the outcomes of the randomized clinical trial but call for additional research to overcome its limitations, such as the small participant size, and examine differences in metabolic parameters. 

The researchers conclude that “any effects of time-restricted eating on weight in prior studies may be due to reductions in caloric intake.” They found no differences in glycemic measures from the different eating patterns. 

A form of intermittent fasting, time-restricted eating, has emerged as a method for weight loss — limiting eating to a specific time and fasting for the remainder of the day — which helps to reduce daily caloric intake. 

Commenting on the study, Dr. Adam Collins, associate professor of nutrition from the University of Surrey, UK, says that the study helps confirm the usefulness of time-restricted eating as a potential intervention for favorable dietary change. 

Moreover, he adds that the trial hints at other benefits that warrant further study, specifically regarding metabolic parameters — like insulin, blood lipids, glucose and glycemia — affected by weight loss and intermittent fasting.

“The failure of this new study to show any differences in these metabolic parameters is likely due to the study being underpowered for these variables, especially given that many of these are not sensitive enough markers of change (e.g., fasted insulin, glucose). Failure to see differences is also majorly impacted by including diabetic and non-diabetic individuals within the groups, which will likely obscure differences in glycemia that may be seen.”

Study set up 
Researchers from John Hopkins University randomly assigned the trial’s 41 participants with obesity and prediabetes to either a time-restricted eating pattern with a ten-hour eating window or to a regular eating pattern for 12 weeks. The results are published in the Annals of Internal Medicine. 

The time-restricted eating group consumed foods between 8am and 6pm, with most of their calories eaten before 1pm. Meanwhile, the other group ate between 8am and midnight, consuming at least 50% of all calories after 5pm. 

The time-restricted eating group consumed foods between 8am and 6pm, with most of their calories eaten before 1pm.Both groups received prepared meals with identical macronutrient and micronutrient compositions and instructions on when to consume these. 

After three months, the time-restricted eating group lost an average of 2.3 kg, and the participants on a usual eating pattern lost an average of 2.6 kg per participant. The researchers found no changes in fasting glucose, insulin resistance, glucose tolerance, blood pressure, lipid levels and waist circumference. 

Collins adds that previous evidence indicates that alternate-day fasting or 5:2 models of intermittent fasting create an overall calorie deficit and lead to significant weight loss “comparable to or better than traditional daily calorie restriction.” 

“Similarly, previous studies on time-restricted eating have commonly observed weight loss as an outcome, despite no prescribed calorie restriction, likely due to changes in diet behavior due to restricting the eating window.” 

Metabolic differences 
At the same time, Collins asserts studies still need to show clear differences in metabolic rate and energy cost of digesting food linked to meal timing, which he explains are partly due to methodological issues in reliably measuring these. 

He notes that the trial can help find the independent metabolic effects of fasting due to the “careful matching of calories and macronutrient intake of the time-restricted eating and control universal eating pattern groups, through the use of supplied packaged meals.”

However, this would require a stronger focus on metabolic parameters of insulin, blood lipids, glucose and glycemia, for which the study found no differences. 

“These [metabolic parameters] are known to change favorably in response to weight loss (reduction of adiposity), particularly in those overweight, with obesity, diabetes/prediabetes, or those with cardiometabolic risk factors (dyslipidemia, hypertension, etc.).”

“Yet, these parameters have also been shown in previous studies to change in response to ‘intermittent fasting.’ Indeed, there is much existing mechanistic evidence to demonstrate the metabolic benefits of meal timing and fasting.” 

Collins adds that an earlier randomized controlled trial he conducted that examined continuous energy restriction versus intermittent energy restriction, matched for weight loss, “showed benefits of metabolic handling following intermittent fasting not seen in the other group, particularly in terms of lipid handling.” 

Follow-up research should examine metabolic parameters, such as insulin, blood lipids, glucose and glycemia.Professor Nita Forouhi from the MRC Epidemiology Unit at the University of Cambridge, UK, agrees that the study’s findings for the secondary outcomes of metabolic parameters are inconclusive. 

“For instance, the results for improvements in markers of glucose control seemed to be greater in the time-restricted eating group, but the sample size was not likely adequate to identify between-group differences. The measurement of glycated hemoglobin would have been useful but was omitted in error though it was prespecified.” 

“The use of continuous glucose monitoring is now readily available and would have contributed meaningfully to understanding a more granular effect of the two interventions on whether and how much the glucose levels change over the timing of eating, but this was not included.”

Limitations and follow-up
Forouhi also comments that the scientific understanding of time-restricted eating is not entirely understood, with many remaining unanswered questions. 

“There were several problems that may limit reaching firm conclusions beyond the issues of small sample size and short duration already acknowledged by the authors.” 

“It is questionable whether randomization worked effectively, with several parameters not equally distributed in the two study groups. The authors acknowledged that participants had substantially greater average weight in the usual eating pattern group (103.7 kg) than the time-restricted eating group (95.6 kg) and tested its impact in ancillary analysis. Still, other factors were ignored, such as notable differences in the two groups for markers of glucose and insulin, cholesterol and systolic blood pressure.” 

She adds that energy intake information is not provided. However, it seems that physical activity energy expenditure was “notably reduced” in the time-restricted eating group, with an average of 34 minutes lower time spent active and around 430 lower activity counts per day than the usual eating pattern group. 

Moreover, Forouchi cautions that the “generalizability of the findings to men and other ethnic groups will need exploring given that 93% of the sample were black women.” 

Research published earlier this year suggested that cycles of a fasting-mimicking diet may reduce insulin resistance, liver fat, immune system aging and biological aging. 

At the same time, intermittent fasting has recently been linked to an increased risk of cardiovascular death, although scientists dispute these findings, pointing to data limitations in the study.

By Jolanda van Hal