Effects of a 12-Week Mediterranean-Type Time-Restricted Feeding Protocol in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomised Controlled Trial-The 'CHRONO-NAFLD Project'.

Triada Bali, Sofia Tsitsou, Evangelos Cholongitas, Kalliopi-Anna Poulia, Emilia Papakonstantinou, Dimitrios S Karagiannakis, Magdalini Adamantou, Aristi Saridaki

Journal: Alimentary pharmacology & therapeutics 2025;61(8):1290-1309

PMID: 40017349

Plain Language Summary

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Diet and lifestyle changes are essential to the management of metabolic dysfunction-associated steatotic liver disease (MASLD). The Mediterranean diet (MD) is known for its health benefits, particularly for liver health, while time restricted feeding (TRF) involves eating within a specific time window each day. This 12-week randomised controlled trial aimed to see how this combination could impact the health of individuals with MASLD compared to a hypercaloric MD only.

The findings suggested that following a hypocaloric (lower calorie) Mediterranean diet alone lead to improvements in liver health and metabolic markers. However when this diet was combined with TRF, further improvements were seen to blood sugar control.

It was concluded that the MD was a diet that can benefit those with MASLD especially when it was combined with TRF. This study could be used by healthcare professionals to understand the potential benefits of combining a Mediterranean diet with time-restricted feeding for patients with metabolic dysfunction-associated steatotic liver disease. TRF was most effective when it was performed from 8am-6pm.

Expert Review

Reviewer: Chloe Steele
1st Oct 2025
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Conflict of interest

None

Take home message

• Nutritional intervention is an effective way to help manage MASLD.    • The MD may be easy to follow and an effective way to improve body weight, glucose metabolism, blood lipids, blood pressure, and liver steatosis but at the potential detriment to muscle.

• Adding in eTRF or lTRF may respectively have additional benefits to glucose metabolism and blood lipid levels.

Evidence category

B: Systematic reviews including RCTs of limited number

Summary review

Introduction

• Metabolic dysfunction-associated steatotic liver disease (MASLD) could be managed nutritionally through the adoption of a Mediterranean diet (MD) or the adoption of time restricted feeding (TRF).

• This study aimed to determine the effects of 10-hour TRF in combination with the MD, compared to an unrestricted MD in obese and overweight individuals with MASLD and to assess whether  the timing of TRF affects outcomes.


Methods

• This was a randomised control trial of 59 individuals with MASLD and overweight/obesity split into:

• Control (n=19) – hypercaloric MD only

•  Early TRF (eTRF) (n=20) – hypercaloric MD plus restricted eating between 8am-6pm.

•  Late TRF (lTRF) (n=20) – hypercaloric MD plus restricted eating between 12pm-10pm.

• 12-week study.


Results

Compared to baseline:

• All groups exhibited similar body weight (7.6%–8.3%) and fat mass loss (14.8%–16.7%) by the end of the trial (P=>0.05). Muscle mass also decreased similarly across the groups.

• All groups had improved glucose metabolism. However, HOMA-IR (eTRF: P= 0.001, control: P=0.024), and Matsuda index (P=0.021, P=0.014), were not improved in the lTRF group.

•Lipids were different between the groups (P=<0.05), with control having improved low density lipoprotein (LDL) (P=0.002), and atherogenic index (P=0.046), and control and ITRF having improved total cholesterol (P=0.002 and P=0.009 respectively). These changes were not seen with eTRF.

• Systolic and diastolic blood pressure was improved in all groups (P=<0.05 for all).

• All groups showed improvements to liver steatosis (6.5%-9.5%) (P=<0.05 for all).


Conclusion

The MD is of benefit to metabolic and anthropogenic outcomes in individuals with MASLD. Combining this with an eTRF pattern of eating could aid further improvements to glucose metabolism.

Clinical practice applications

• The MD may be an easy-to-follow diet that may benefit anthropometric and biochemical measurements in individuals with MASLD regardless of whether TRF protocols are followed.

• However, the addition of eTRF may have further benefits to glucose metabolism and lTRF may be of further benefit to blood lipid levels.

Considerations for future research

•  This study investigated individuals with MASLD and obesity. Future studies could investigate how the MD and TRF affect other comorbidities regularly observed with MASLD such as type 2 diabetes, hypertension, and lipidaemia.

• Muscle loss was observed in all groups and the effects of combining the MD, TRF, and weight resistance exercise would be of interest.

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Abstract

BACKGROUND

The Mediterranean diet (MD) is considered the best dietary approach for patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, time-restricted feeding (TRF) has gained attention for its lifestyle compatibility and health benefits.

AIMS

This study aimed to compare the effects of a hypocaloric MD with a 10-h TRF protocol to an unrestricted MD in MASLD patients with overweight/obesity and evaluate differences between early and late TRF.

METHODS

This 12-week randomised controlled trial in MASLD patients with overweight/obesity consisted of three groups, all following a hypocaloric Mediterranean-type diet. The control group had no eating time restrictions. The early TRF (eTRF) and late TRF (lTRF) groups had a 10-h eating window, from 8 AM to 6 PM and from 12 PM to 10 PM, respectively. Various health parameters were measured. Compliance was tracked via food diaries, and an 8-week follow-up occurred post-intervention.

RESULTS

Fifty-nine MASLD individuals (27 males; 52.9 years; body mass index 32.1 kg/m) completed the trial (control, n = 19; eTRF, n = 20; lTRF, n = 20). All groups showed significant 12-week reductions in body weight, anthropometry and blood pressure. Glycated haemoglobin A and insulin resistance, as measured by the Matsuda index, homeostatic model assessment for insulin resistance and fasting glucose-to-insulin ratio, improved in the eTRF group at 12 weeks.

CONCLUSIONS

This study corroborates the efficacy of MD in ameliorating cardiometabolic risk factors such as body weight and blood pressure in MASLD patients. The combination with an eTRF protocol may improve glycaemic control (NCT05866744).

TRIAL REGISTRATION

The study is registered at clinicaltrials.gov (NCT05866744).

© 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Address: Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, Agricultural University of Athens, Athens, Greece.; First Department of Internal Medicine, Laiko General Hospital of Athens, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Fourth Department of Internal Medicine, Attiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Patient Centred Factor

Laboratory Testing

Modifiable Lifestyle Factors

Jadad Score

Allocation Concealment

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