Exercise Training Reduces Liver Fat in Patients With NAFLD, Even Without Weight Loss

Carolyn Crist

February 13, 2023

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)-minutes/week — or 150 minutes per week of brisk walking — was required to achieve a treatment response, independently of weight loss.

Dr Jonathan Stine

"In the absence of a regulatory agency-approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD," first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the Fatty Liver Program at the Penn State Health Milton S. Hershey Medical Center, in Hershey, Pennsylvania, told Medscape Medical News.

"With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss," Stine said. "And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?" He noted that this analysis is a step toward helping to answer these questions.

The study by Stine and his colleagues was published online in The American Journal of Gastroenterology.

Analyzing Studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors write. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg2. The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7% to 10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was -6.7% for the 338 participants enrolled in exercise training, compared with -0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training vs the control was -5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants ― 118 participants in exercise training, and 77 control participants. The mean relative change was -24.1% among the exercise training group and +7.3% among the control group. The pooled mean difference in relative change for exercise training vs the control was -26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a -8% absolute and -28.9% relative mean difference in MRI-measured liver fat, compared with -4.1% and -22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

"Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology," Stine said. "Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction."

Ongoing Research

Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

"Importantly, this new study we're undertaking is designed to mimic a real-world setting in which people's daily schedules are highly variable," he said. "Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise."

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors write. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they write.

"The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver," Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri in Columbia, told Medscape Medical News.

Kanaley, who wasn't involved with this study, has researched exercise training among patients with NAFLD. She and colleagues have found that moderate-intensity and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

"So often, people get frustrated with exercise if they do not see weight loss," she said. "But in this case, there seems to be benefits of the exercise, even without weight loss."

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Kanaley reported no relevant financial relationships.

Am J Gastroenterol. Published January 30, 2023. Abstract

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.

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