Ad libitum mediterranean and low-fat diets both significantly reduce hepatic steatosis: a randomized controlled trial
Abstract
Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors, regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets (Mediterranean [MD] or low fat [LF]) on hepatic steatosis (HS) and cardiometabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs. LF). HS was determined by magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat, but lower carbohydrate and sodium, intakes compared to LF subjects (P < 0.01). At week 12, HS had reduced significantly in both groups (P < 0.01), and there was no difference in liver fat reduction between groups (P = 0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups (-1.6 [±2.1] kg in LF vs -2.1 [±2.5] kg in MD; P = 0.52). Within-group improvements in Framingham Risk Score (FRS), total cholesterol, serum triglyceride (TG), and glycated hemoglobin (HbA1c) were observed in the MD (all P < 0.05), but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%; P = 0.048). Conclusion: Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree.
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In patients with MASLD/MASH, the Mediterranean diet significantly reduced BMI compared with standard care or control diet (WMD = -0.70 kg/m2, 95% CI -1.03 to -0.36, P < 0.001).
“In total, seven studies reported data revealed that the MD significantly reduced BMI [56–60, 62, 64](WMD = − 0.70 kg/m2, 95% CI = − 1.03 to − 0.36, P < 0.001)”
In patients with MASLD/MASH, the Mediterranean diet significantly reduced weight compared with standard care or control diet (WMD = -2.38 kg, 95% CI -4.11 to -0.66, P = 0.01).
“The overall results showed that the MD significantly reduced weight [weighted mean difference (WMD = − 2.38 kg, 95% CI − 4.11 to − 0.66, P = 0.01) in comparison to standard care or control diet.”
In patients with MASLD/MASH, the Mediterranean diet significantly reduced waist circumference compared with standard care or control diet (WMD = -1.56 cm, 95% CI -3.02 to -0.09, P = 0.04).
“and WC [56–60, 62, 64] (WMD = − 1.56 cm, 95% CI = − 3.02 to − 0.09, P = 0.04) in comparison to standard care or control diet”
In patients with MASLD/MASH, the Mediterranean diet significantly reduced ALT levels (WMD = -3.96 IU/L, 95% CI -6.54 to -1.38, P < 0.001).
“the overall results of six RCTs [56, 57, 59, 60, 62, 63] showed a significant effect of the MD on ALT levels (WMD = − 3.96 IU/L, 95% CI = − 6.54 to − 1.38, P < 0.001).”
Another RCT showed no changes in liver steatosis between the two groups.
“However, another RCT showed no changes in liver steatosis between the two groups [56].”
Among RCTs on the Mediterranean diet, three were low risk, seven had some concerns, and two were high risk of bias.
“Regarding the RCTs on the MD, three were defined as “Low Risk” [56, 60]; seven studies were defined as “Some concerns” [28, 55, 57, 59, 61, 62, 64]; and two studies were defined as “High-Risk” [58, 63].”
In a meta-analysis of observational studies and clinical trials, the Mediterranean diet has repeatedly been shown to provide hepatic and cardiovascular health benefits, even without weight loss.
“In a meta-analysis of observational studies and clinical trials, the Mediterranean diet has repeatedly been shown to provide hepatic and cardiovascular health bene fi ts, 296,297 even without weight loss. 298”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [298]
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References 41 · Cited by 227
- Authors
- Properzi, C., O'Sullivan, T. A., Sherriff, J. L., Ching, H. L., Jeffrey, G. P., Buckley, R. F., Tibballs, J., MacQuillan, G. C., Garas, G., & Adams, L. A.
- Affiliations
- Edith Cowan University (AU)
- School of Medical and Health Science,Edith Cowan University,Joondalup,Australia
- Curtin University (AU)
- The University of Western Australia (AU)
- Harvard University (US)
- Sir Charles Gairdner Hospital (AU)
- Corresponding author
- Adams, Leon A.
- ORCID
- Venue
- Hepatology
- Published
- 2018-10-14
- Volume
- 68
- Issue
- 5
- Pages
- 1741-1754
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2799372743
- Cited by
- 227
- References
- 41
- Citations by year
- 2026: 19 · 2025: 50 · 2024: 24 · 2023: 31 · 2022: 19 · 2021: 27 · 2020: 29 · 2019: 25 · 2018: 3
- FWCI
- 16.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- eSpace (Curtin University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- non-alcoholic fatty liver disease, hepatic steatosis, Mediterranean diet, low-fat diet, cardiometabolic risk factors, dietary intervention, weight loss, dietary adherence, liver fat reduction, Framingham risk score, serum triglycerides, HbA1c
- MeSH terms
- Anthropometry, Female, Humans, Liver, Male, Middle Aged, Magnetic Resonance Spectroscopy, Patient Compliance, Prospective Studies, Quality of Life, Risk Factors, Weight Loss, Single-Blind Method, Treatment Outcome, Diet, Fat-Restricted, Diet, Mediterranean, Vascular Stiffness, Non-alcoholic Fatty Liver Disease
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