The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease
Open accessAbstract
Background & aims Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques.Methods Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS).Results At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets).Conclusions Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.
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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)”
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 [57]
The Results section states that there was no change in BMI between the Mediterranean and comparison diet periods. It also reports that the difference in weight change was not significant. This trial therefore does not support a significant BMI reduction; the quoted WMD is a pooled estimate from seven studies, not a result reported by this paper. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredIn 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.”
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 [57]
The Results report that weight loss was small and that the difference in weight change between the Mediterranean and comparison diets was not significant (p=0.1). The paper does not report the claimed weighted mean difference or confidence interval; its weight finding is contrary to the attributed significant reduction. (LLM, conf=0.91)
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Experimental — accuracy not yet measuredIn 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”
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 [57]
The Results report no change in waist circumference between the Mediterranean and low-fat/high-carbohydrate diet periods, contrary to a significant reduction in this trial. The cited paper does not report the stated WMD; that figure appears to be a pooled estimate from the citing document. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredTwo studies reported significantly lower liver fat percentages in the Mediterranean diet group compared to either a low-fat-high-carbohydrate diet or a standard control group.
“while two others reported significantly lower liver fat percentages in the MD group compared to either a low-fat–high-carbohydrate diet [57] or a standard control group [64].”
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).”
In a crossover randomized controlled trial of twelve non-diabetic subjects with biopsy-proven MASLD, adherence to the Mediterranean diet led to a reduction in hepatic steatosis and an improvement in insulin sensitivity even in the absence of weight loss.
“Notably, the findings demonstrated that, even in the absence of weight loss, adherence to the Mediterranean diet led to a reduction in hepatic steatosis and an improvement in insulin sensitivity (102).”
From Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility (2024) · cites this paper as [102]
Randomized controlled crossover trials defined the superiority of the Mediterranean diet in the improvement of insulin sensitivity, metabolic parameters, and steatosis over low-fat diets.
“Cross-sectional and longitudinal reports evidenced a lower likelihood of NASH in patients who were adherent to the MedDiet [75,76], whereas randomized controlled crossover trials defined the superiority of this diet in the improvement of insulin sensitivity, metabolic parameters and steatosis over low-fat ones [77,78].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [77]
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- Authors
- Ryan, M. C., Itsiopoulos, C., Thodis, T., Ward, G., Trost, N., Hofferberth, S., O’Dea, K., Desmond, P. V., Johnson, N. A., & Wilson, A. M.
- Affiliations
- St Vincent's Hospital Melbourne (AU)
- La Trobe University (AU)
- University of South Australia (AU)
- The University of Sydney (AU)
- Corresponding author
- Ryan, Marno C.
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 59
- Issue
- 1
- Pages
- 138-143
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2053985254
- Cited by
- 778
- References
- 46
- Citations by year
- 2026: 39 · 2025: 59 · 2024: 66 · 2023: 90 · 2022: 66 · 2021: 71 · 2020: 77 · 2019: 70 · 2018: 69 · 2017: 52 · 2016: 50 · 2015: 26 · 2014: 29 · 2013: 12
- FWCI
- 28.42
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council
- 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
- Mediterranean diet, non-alcoholic fatty liver disease, hepatic steatosis, insulin sensitivity, monounsaturated fatty acids, low-fat high-carbohydrate diet, dietary intervention, hyperinsulinemic-euglycemic clamp, 1H magnetic resonance spectroscopy, weight loss, insulin resistance
- MeSH terms
- Adult, Aged, Fatty Liver, Female, Humans, Insulin Resistance, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Glucose Clamp Technique, Cross-Over Studies, Diet, Mediterranean, Lipid Metabolism, Obesity, Abdominal, Non-alcoholic Fatty Liver Disease
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