Intermittent Fasting Plus Exercise a Good Option for Fatty Liver

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD, but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois Chicago and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance, and increasing insulin sensitivity, among patients with obesity and NAFLD, versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois Chicago, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

Around Two Thirds of People With Obesity Have NAFLD

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.

• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.

• Fasting plus exercise group.

• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%), and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), and so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Varady has reported receiving author fees from the Hachette Book Group for the book entitled, “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

Cell Metab. 2023;35:56-70.e3. Abstract

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