Alternate Day Fasting, Exercise, and NAFLD

Alternate Day Fasting Combined With Exercise for the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD)

Approximately 65% of obese individuals have non-alcoholic fatty liver disease (NAFLD), and this condition is strongly related to the development of insulin resistance and diabetes. Innovative lifestyle strategies to treat NAFLD are critically needed. The proposed research will demonstrate that alternate day fasting (ADF) combined with exercise is an effective non-pharmacological therapy to treat NAFLD.

Study Overview

• Status: Completed
• Conditions: Obesity; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Other: Alternate day fasting; Other: Exercise

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is characterized by an accumulation of fat in the liver (not resulting from excessive alcohol consumption). Approximately 65% of obese individuals have NAFLD, and this condition is strongly related to the development of insulin resistance and type 2 diabetes. While certain pharmacological agents have been shown to reduce liver fat (i.e. thiazolidinediones), there is mounting concern regarding the safety and weight-gaining effects of these compounds. In light of this, recent research has focused on non-pharmacological lifestyle therapies to reduce hepatic steatosis, such as daily calorie restriction combined with aerobic exercise. Evidence from clinical trials suggest that this combination is an effective lifestyle therapy improve liver fat content and hepatic insulin sensitivity.

More recently, it's been shown that intermittent fasting may produce even greater improvements in hepatic steatosis and hepatic insulin sensitivity, when compared to conventional calorie restriction. For instance, intrahepatic lipid accumulation was lower and insulin sensitivity was higher in mice fasted every other day, when compared to mice who were energy restricted every day. Moreover, data from human trials show that adults with obesity experience greater decreases in insulin and insulin resistance with intermittent fasting versus daily restriction. These findings suggest that intermittent fasting may be a more effective diet therapy to reduce hepatic steatosis and improve insulin sensitivity, when compared to daily calorie restriction. Although these findings are very promising, these data still require confirmation by a randomized controlled clinical trial.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

INCLUSION CRITERIA:

• Age between 18 to 65 years old
• BMI between 30.0 and 59.9 kg/m2
• NAFLD (hepatic steatosis ≥ 5% confirmed by MRI-PDFF)
• Sedentary (<20 min, 2x/week of light activity at 3-4 metabolic equivalents (METs) for 3 mo prior to study)

EXCLUSION CRITERIA:

• Have chronic liver disease other than NAFLD (hepatitis B or C, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
• Consume excessive amounts of alcohol women: 70 g of ethanol (5 alcoholic drinks per week) and men 140 g of ethanol (10 drinks per week) in the past 6 months)
• Have a history of known cardiovascular, pulmonary or renal disease
• Diagnosed T1DM or T2DM
• Are not weight stable for 3 months prior to the beginning of study (weight gain or loss > 4 kg)
• Are claustrophobic or have implanted metallic/electrical devices (e.g. cardiac pacemaker, neuro-stimulator)
• Are taking drugs that induce steatosis (e.g. corticosteroids, estrogens, methotrexate, Ca channel blockers)
• Are taking drugs that benefit NAFLD (e.g. betaine, pioglitazone, rosiglitazone, metformin, or gemifibrozil)
• Are taking drugs that influence study outcomes (weight loss medications)
• Are perimenopausal or have an irregular menstrual cycle (menses that does not appear every 27-32 days)
• Are pregnant, or trying to become pregnant
• Are smokers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alternate day fasting; These participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days".	Other: Alternate day fasting; The diet involves consuming 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days".
Experimental: Exercise; These participants will participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.	Other: Exercise; The exercise intervention involves supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.
Experimental: Combination alternate day fasting plus exercise; These participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". They will also participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.	Other: Alternate day fasting; The diet involves consuming 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days".; Other: Exercise; The exercise intervention involves supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.
No Intervention: Control; Controls will be instructed to maintain their weight throughout the trial, and not to change eating or physical activity habits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hepatic Steatosis	Hepatic steatosis will be measured by magnetic resonance imaging (MRI-PDFF)	Change from week 1 to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alanine Aminotransferase (ALT)	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Change in Aspartate Aminotransferase (AST)	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Change in HbA1c	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Change in Body Weight	Measured by digital scale	Change from week 1 to week 12
Change in Fasting Glucose	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Change in Fasting Insulin	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Change in Insulin Resistance	Measured by Homeostatic model assessment of insulin resistance (HOMA-IR). The HOMA-IR value was calculated using the formula: [HOMA-IR = glucose (mg/dL) × insulin (mU/L)/405]. Interpretation of HOMA-IR Scores: < 1.0: Normal insulin sensitivity; 1.0-1.9: Mild insulin resistance; > 2.0: Moderate to severe insulin resistance.	Change from week 1 to week 12

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Krista Varady, PhD, University of Illinois Chicago

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): May 1, 2024
• Study Completion (Actual): May 1, 2024

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Digestive System Diseases; Liver Diseases; Overweight; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Non-alcoholic Fatty Liver Disease; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: 2019-0300; R01DK119783 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No