Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial

Mark Ezpeleta, Kelsey Gabel, Sofia Cienfuegos, Faiza Kalam, Shuhao Lin, Vasiliki Pavlou, Zhenyuan Song, Jacob M. Haus, Sean Koppe, Shaina J. Alexandria, Lisa Tussing-Humphreys, Krista A. Varady*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Innovative non-pharmacological lifestyle strategies to treat non-alcoholic fatty liver disease (NAFLD) are critically needed. This study compared the effects of alternate day fasting (ADF) combined with exercise to fasting alone, or exercise alone, on intrahepatic triglyceride (IHTG) content. Adults with obesity and NAFLD (n = 80, 81% female, age: 23–65 years) were randomized to 1 of 4 groups for 3 months: combination of ADF (600 kcal/2,500 kJ “fast day” alternated with an ad libitum intake “feast day”) and moderate-intensity aerobic exercise (5 session per week, 60 min/session); ADF alone; exercise alone; or a no-intervention control group. By month 3, IHTG content was significantly reduced in the combination group (−5.48%; 95% CI, −7.77% to −3.18%), compared with the exercise group (−1.30%; 95% CI, −3.80% to 1.20%; p = 0.02) and the control group (−0.17%; 95% CI, −2.17% to 1.83%; p < 0.01) but was not significantly different versus the ADF group (−2.25%; 95% CI, −4.46% to −0.04%; p = 0.05). Body weight, fat mass, waist circumference, and alanine transaminase (ALT) levels significantly decreased, while insulin sensitivity significantly increased in the combination group compared with the control group. Lean mass, aspartate transaminase (AST), HbA1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups. Combining intermittent fasting with exercise is effective for reducing hepatic steatosis in patients with NAFLD but may offer no additional benefit versus fasting alone.

Original languageEnglish (US)
Pages (from-to)56-70.e3
JournalCell Metabolism
Issue number1
StatePublished - Jan 3 2023


  • aerobic exercise
  • alternate day fasting
  • insulin resistance
  • intermittent fasting
  • non-alcoholic fatty liver disease
  • obesity
  • weight loss

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial'. Together they form a unique fingerprint.

Cite this