# Alternate day fasting combined with exercise for the treatment of NAFLD

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $359,775

## Abstract

Project Summary/ Abstract
Background: 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. Alternate day fasting (ADF) has been shown in animals to
reduce hepatic steatosis and improve hepatic insulin sensitivity, but these findings have yet to be confirmed in
human subjects. ADF consists of a “feast day” where individuals are permitted to consume food ad libitum,
alternated with a “fast day” where individuals consume 25% of their usual intake (~500 kcal). We recently
performed a pilot study to evaluate the effects of ADF combined with exercise, versus ADF or exercise alone,
on hepatic parameters in prediabetic NAFLD patients. Our results show that the combination of ADF plus
exercise produced greater reductions in alanine aminotransferase (ALT; an indirect marker of hepatic
steatosis), compared to ADF alone, or exercise alone, after 12 weeks. Greater decreases in insulin resistance,
HbA1c, LDL cholesterol, and more pronounced increases in HDL cholesterol, were observed in the
combination group versus individual interventions. Data from our pilot trial also suggest that these decreases in
insulin resistance may be mediated in part by changes in hepatocyte-derived hormones (hepatokines) that
occur with liver fat reduction. Although these pilot findings are very promising, these data still require
confirmation by a well powered longer-term (24 week) clinical trial. Hypotheses: The present proposal will test
the following hypotheses: (1) The combination group (ADF plus exercise) will experience greater reductions in
hepatic steatosis (measured by magnetic resonance spectroscopy; MRS) when compared to ADF or exercise
alone; (2) The combination group will experience greater improvements in hepatokine profile (fetuin-A, fetuin B,
FGF-21, RBP4, selenoprotein P, SHBG, adropin) when compared to ADF or exercise alone; (3) The
combination group will experience greater improvements in hepatic insulin sensitivity, insulin resistance and
HbA1c and other metabolic disease risk variables (fasting glucose, fasting insulin, triglycerides, LDL
cholesterol, LDL particle size, blood pressure, inflammatory parameters) when compared to ADF or exercise
alone. Methods: To test these objectives, a 24-week randomized, controlled, parallel-arm feeding trial will be
implemented. Obese prediabetic individuals with NAFLD (n = 180) will be randomized to 1 of 4 groups:
(1) ADF (fast day: 25% energy intake, feed day: ad libitum fed, no exercise), (2) exercise (ad libitum fed,
training 5 days/week supervised), (3) combination (ADF plus exercise), and (4) control (ad libitum fed, no
exercise). Significance: If the aims of this application are achieved, this study will be the first to show that the
combination of alternate day fasting plus aerobic exercise is an effective non-pharmacologi...

## Key facts

- **NIH application ID:** 10411982
- **Project number:** 5R01DK119783-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Krista Amy Varady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $359,775
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411982

## Citation

> US National Institutes of Health, RePORTER application 10411982, Alternate day fasting combined with exercise for the treatment of NAFLD (5R01DK119783-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10411982. Licensed CC0.

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