Background: Approximately 65% of individuals with obesity have nonalcoholic fatty liver disease (NAFLD) . The primary treatment for NAFLD is regulating weight per diet and exercise. Alternate day fasting (ADF) has been shown to improve body composition and cardiometabolic risk factors in animals. This is the first human trial to compare the effects of ADF plus endurance exercise, ADF alone, endurance exercise alone versus a no intervention control, on body weight and metabolic disease risk factors in participants with obesity and NAFLD.

Methods: Subjects with obesity and NAFLD (n = 48) were randomized to 1 of 4 groups for 12 weeks:

  • 1) ADF (600 kcal “fast day”, alternated with an ad libitum intake “feast day”) ,

  • 2) exercise (endurance exercise 5 times/week for 60 min/d) ,

  • 3) combination (ADF + exercise) ,

  • or 4) control (usual diet) .

Results: Body weight was reduced (P < 0.05) in the ADF group (-5.3 ± 1.0 %) and combination group (-4.9 ± 0.6 %) , but not the exercise group (-1.9 ± 0.6 %) , versus controls (-0.3 ± 1.2 %) . ALT was reduced (P < 0.05) in the combination group (-29 ± 9%) , but not in the ADF group (-9 ± 8%) , exercise group (1 ± 3%) , versus controls (17 ± 10%) . No significant changes were observed for liver fat, body composition, AST, lipid markers, or glucoregulatory factors. Subjects in the ADF and combination groups were adherent with the fast day energy goal (600 kcal) at week 12 (ADF: 548 kcal; combination: 657 kcal) . Subjects in the exercise and combination groups were adherent with attending the 5 workout sessions per week (exercise: 79% attendance; combination: 83% attendance) .

Conclusion: These preliminary findings suggest that combination of ADF plus exercise and ADF alone may be effective non-pharmacological therapies to reduce body weight and ALT. However, neither combination intervention nor ADF alone have had any effect on liver fat, metabolic risk factors, or glucoregulatory factors such as insulin.


K. Gabel: None. K. Varady: None. S. Cienfuegos: None.


NIH/NIDDK (R01DK119783-03)

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