Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
No differences were found in waist circumference for aerobic exercise interventions compared to control.
“Nine aerobic interventions reported WC [69–72, 74, 75, 78, 79, 90], but no differences were found in comparison to control”
From Effects of Mediterranean diet, exercise, and their combination on body composition and liver outcomes in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [70]
The Results section (page unavailable) reports that waist circumference fell significantly more with the combined aerobic-exercise and fasting intervention than with control (P < 0.01), contrary to the blanket claim of no differences for aerobic interventions. The passage does not report a direct exercise-alone versus control comparison. (LLM, conf=0.78)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThere is currently very little evidence for a beneficial effect of time-restricted eating over regular caloric restriction on hepatic lipid content in individuals with MASLD.
“There is currently very little evidence for a bene fi cial effect of timerestricted eating over regular caloric restriction on hepatic lipid content in individuals with MASLD. 283,288,294”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [283]
The Discussion reports comparable reductions in intrahepatic triglyceride content for a cited intermittent-fasting regimen and daily calorie restriction, and calls for more direct comparisons. That supports caution about claiming an advantage over calorie restriction, but this paper studies alternate-day fasting, not time-restricted eating specifically; its own trial had no calorie-restriction comparison group. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThere is limited data on long-term dietary interventions in MASLD since study durations range from 2-24 months.
“There is limited data on long-term dietary interventions in MASLD since study durations range from 2-24 months. 283 -285”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [283]
The Discussion > Limitations section says this trial lasted three months and that the long-term effects of intermittent fasting, alone or with exercise, on NAFLD warrant investigation. It does not establish that MASLD dietary-intervention studies generally range from 2 to 24 months; that duration range is unsupported by this source. Page numbers were unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome studies report that combining fasting with exercise, including resistance training, is effective for preserving or increasing lean body mass while achieving weight loss.
“Some studies have explored combining fasting with exercise, including resistance training, reporting the effectiveness of preserving [32, 85, 86] or even increasing [73] lean body mass while achieving weight loss simultaneously”
From Comparing caloric restriction regimens for effective weight management in adults: a systematic review and network meta-analysis (2024) · cites this paper as [85]
All RCTs on aerobic exercise showed no difference in liver fibrosis indices/stages between aerobic exercise and control.
“With regard aerobic exercise, all RCTs showed no difference between liver fibrosis indices/stages between the aerobic exercise group and the control group [68, 70, 72, 74, 75].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 108 · Cited by 181
Research works printed but not linked: 4
- [70]Eyth E, Naik R (2022). NIH StatPearls. Hemoglobin A1C. https://www.ncbi.nlm.nih.gov/books/NBK549816/. 31747223
- [102]Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, and Pol S (2007). FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 46, 32– 36. 10.1002/hep.21669. 17567829 · DOI
- [105]Huber P (1967). Under nonstandard conditions. In Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability.
- [106]White H (1980). A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity. Econometrica: journal of the Econometric Society, 817– 838.
- Authors
- Ezpeleta, M., Gabel, K., Cienfuegos, S., Kalam, F., Lin, S., Pavlou, V., Song, Z., Haus, J. M., Koppe, S., Alexandria, S. J., Tussing-Humphreys, L., & Varady, K. A.
- Affiliations
- University of Illinois Chicago (US)
- University of Michigan (US)
- Northwestern University (US)
- Corresponding author
- Varady, Krista A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 35
- Issue
- 1
- Pages
- 56-70.e3
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC9812925
- OpenAlex
- W4312114234
- Cited by
- 181
- References
- 108
- Citations by year
- 2026: 51 · 2025: 49 · 2024: 55 · 2023: 26
- FWCI
- 22.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (R01DK119783)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- non-alcoholic fatty liver disease, alternate-day fasting, intermittent fasting, aerobic exercise, hepatic steatosis, intrahepatic triglyceride, obesity, insulin sensitivity, lifestyle intervention, alanine aminotransferase, hepatokines
- MeSH terms
- Adult, Aged, Body Weight, Fasting, Female, Humans, Liver, Male, Middle Aged, Triglycerides, Exercise, Young Adult, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
