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Adding time-restricted eating to a calorie-restricted diet did not provide added benefits in adults with obesity and nonalcoholic fatty liver disease (NAFLD), according to the results of a randomized controlled trial conducted in China.

With the same calorie restrictions, an 8-hour time-restricted eating (TRE) pattern was no more effective in lowering intrahepatic triglyceride (IHTG) content or achieving resolution of NAFLD than daily calorie restriction (DCR) without time constraints (habitual meal timing).

TRE also did not provide additional benefits over DCR for reducing body fat or metabolic risk factors.

Calorie intake restriction seems to explain most of the beneficial effects of TRE and supports the importance of calorie restriction in a TRE regimen in adults with obesity and NAFLD, say the investigators, led by Xueyun Wei, coumadin testing device MD, with Southern Medical University in Guangzhou.

The study “supports some other recent data that kind of disproves that intermittent fasting actually works that well and that it basically comes down to calorie restriction,” said Lisa Ganjhu, DO, who wasn’t involved in the research.

“It doesn’t matter when you are calorie restricting; it’s just that you are restricting calories to a certain amount. We know that works,” Ganjhu, a clinical associate professor in the division of gastroenterology and hepatology at NYU Grossman School of Medicine, told Medscape Medical News.

Results of the TREATY-FLD study were published online March 17 in JAMA Network Open.

Calorie Reduction Is Key

NAFLD has become a major worldwide public health challenge, affecting roughly 20%-30% of adults in the general population and more than 70% of adults with obesity and diabetes.

Weight loss through lifestyle modifications has been shown to improve liver fat and metabolic disorders. TRE, a type of intermittent fasting, has garnered attention as a potential alternative to DCR for weight loss. “However, most of the reported benefits of TRE are either ‘untested or under tested’ and can’t isolate the effects of TRE itself,” Wei and colleagues note.

In the TREATY-FLD study, 88 adults (mean age, 32 years; 56% male) with obesity and NAFLD and similar baseline characteristics were randomly allocated to a TRE or DCR group.

All participants were instructed to maintain a diet of 1500-1800 kcal/day for men and 1200-1500 kcal/day for women for 12 months. The diets consisted of 40%-55% carbohydrate, 15%-20% protein, and 20%-30% fat. Participants were also given one protein shake per day for the first 6 months and received dietary counseling throughout the study.

Participants in the TRE group were told to eat only between 8 AM and 4 PM each day. Only noncaloric beverages were permitted outside of the daily eating window. Participants in the DCR group had no restrictions on when they could eat.

Investigators found no significant between-group differences in change in MRI-measured IHTG content from baseline to 6 or 12 months (the primary outcome).

At 6 months, IHTG content was reduced by 8.3% in the TRE group and by 8.1% in the DRC group. At 12 months, IHTG content was reduced by 6.9% and 7.9%, respectively. The net change in IHTG content was not significantly different between the groups at 6 months (percentage point difference: −0.2; P = .86) or 12 months (percentage point difference: 1; P = .45)

Liver stiffness was reduced by 2.1 kPa in the TRE group and 1.7 kPa in the DCR group at 12 months, with no significant difference between the groups (P = .33). A percentage of participants in the TRE and DCR groups had resolution of NAFLD (defined as IHTG content <5%) at 12 months (33% vs 49%; P = .31).

During the 12-month intervention, body weight was significantly reduced by 8.4 kg in the TRE group and 7.8 kg in the DCR group, with no significant between-group differences (P = .69).

In addition, waist circumference, body fat percentage, fat mass, lean mass, total abdominal fat, subcutaneous fat, visceral fat, and visceral to subcutaneous fat ratio were all significantly and comparably reduced in the two groups.

Both groups also saw significant and comparable improvement over 12 months in metabolic risk factors, including systolic and diastolic blood pressure, pulse rate, and total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels.

However, TRE might be more effective in improving insulin sensitivity than DCR. Both diets significantly reduced fasting plasma glucose level, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. TRE significantly reduced HOMA-IR compared with DCR at 12 months.

Both diets significantly reduced levels of liver enzymes, including serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase, with no significant between-group differences.

Eat Less, Exercise More

Although the study found no additional benefit from TRE, it’s still good advice to skip snacking in the evening, Ganjhu told Medscape Medical News. “No one snacks on anything healthy at night. I mean, who’s chewing on celery?” she added.

Eating late at night can trigger reflux, so “not eating anything for several hours before bed or better yet going for a walk after dinner to kickstart your metabolism is good advice,” Ganjhu said.

For obesity and fatty liver disease, it really comes down to diet and exercise, she noted.

“For all the money that is going into pharmaceuticals, the long and the short of it is you just have to eat less and work out more and manage all the other factors like diabetes, high blood pressure, and metabolic syndrome. But getting people to follow that is tough,” Ganjhu said.

The study was supported by grants from the National Key Research and Development Project, Joint Funds of the National Natural Science Foundation of China, National Natural Science Foundation of China, and Key-Area Clinical Research Program of Southern Medical University. Wei and Ganjhu report no relevant financial relationships.

JAMA Netw Open. Published online March 17, 2023. Full text

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