Diet and Meal Timing for Non-Alcoholic Fatty Liver Disease

Overseen by Sonal Kumar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Alcohol use, Cirrhosis, Hepatitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial will test if a specific eating pattern can help patients with fatty liver disease more than just following a healthy diet and exercise plan. The goal is to see if this eating pattern can improve liver health by aiding weight loss and better blood sugar control.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on a medication that requires you to eat at specific times, you may need to discuss this with the study team due to the time-restricted eating schedule.

What data supports the effectiveness of the treatment for Non-Alcoholic Fatty Liver Disease?

Research suggests that time-restricted eating and intermittent fasting can improve liver health by reducing liver fat and inflammation, which are key issues in non-alcoholic fatty liver disease. Additionally, lifestyle changes like the Mediterranean diet and increased physical activity have shown significant improvements in liver health. ^{1 2 3 4 5}

Is time-restricted eating or intermittent fasting safe for humans?

Intermittent fasting and time-restricted eating have shown benefits for weight management and liver health, but more studies are needed to confirm their long-term safety in humans. ^{2 5 6 7 8}

How does the treatment of time-restricted eating (TRE) differ from other treatments for non-alcoholic fatty liver disease (NAFLD)?

Time-restricted eating (TRE) is unique because it focuses on limiting the hours during which food is consumed each day, rather than changing the types or amounts of food eaten. This approach may help reduce the risk of NAFLD by aligning eating patterns with natural body rhythms, potentially improving liver health without requiring calorie restriction. ^{2 3 4 5 9}

Research Team

Sonal Kumar, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This study is for adults aged 18-64 with a BMI over 25 and at least 10% liver fat content, who can follow the protocol. It's not for those with other liver diseases, significant alcohol use, recent weight loss of more than 5%, or conditions preventing MRI tests or fasting.

Inclusion Criteria

Must provide signed written informed consent and agree to comply with the study protocol

BMI >25 kg/m²

Baseline liver fat content of at least 10% as measured by MRI-PDFF

Exclusion Criteria

Competing etiologies for hepatic steatosis

I have lost 5% or more of my weight in the last 3 months.

I am mentally capable of understanding and following the study's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a time-restricted eating regimen for 12 weeks, with lifestyle recommendations including a low-calorie diet and moderate-intensity exercise

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat Fibroscan, InBody 770 body composition scan, and MRI-PDFF

4 weeks

Crossover to TRE (optional)

Participants who have not lost sufficient weight may opt to crossover to the TRE arm for another 12-week cycle

12 weeks

4 visits (in-person)

Treatment Details

Interventions

• SOC (Behavioral)
• TRE plus SOC (Behavioral Intervention)

Trial Overview The trial examines time-restricted eating (eating within an 8-hour window) combined with standard care (low-calorie Mediterranean diet and exercise) versus standard care alone on liver fat reduction in non-alcoholic fatty liver disease patients.

Participant Groups

Group I: TRE plus SOC Experimental Treatment 1 Intervention

Participants will be required to fast each day for 12 weeks and will be given lifestyle recommendations with respect to diet and exercise. The registered dietitian (RD) will obtain a baseline dietary record and provide counseling on the time-restricted eating regimen. The RD will collect the participant's normal diet and exercise routine. Counseling will involve instructing the participant to choose an eight-hour eating window (e.g., 10:00am - 6:00pm) during which the participant will be able to eat. During the 16-house fasting window (e.g., 6:00pm - 10:00 am), the participant is able to drink regular water and black coffee or tea. The RD will be available to answer any questions the participants may have pertaining to the regimen and will instruct the participants regarding standard of care lifestyle recommendations. This includes education of a low-calorie diet (500-1000 kcal) and moderate-intensity exercise.

Group II: Crossover to TRE Experimental Treatment 1 Intervention

Participants who have not lost weight or have lost less than or equal to 5% of their body weight, they will be given the option to crossover to the TRE arm. Following the initial 12-week period and end of study MRI, participants would restart another identical 12-week cycle but adhering to the exact steps of the TRE arm including another 4 visits with the registered dieticians (RDs) and an end of study visit with repeat Fibroscan, InBody 770 body composition scan, and MRI-PDFF.

Group III: SOC Active Control 1 Intervention

lifestyle modifications and weight management. Participants will be given lifestyle recommendations with respect to diet and exercise. The registered dietitian (RD) will obtain a baseline dietary record and provide counseling on the time-restricted eating regimen. A baseline dietary record will be assessed prior to fasting initiation with the RD in person. The RD will also collect the subject's normal diet and exercise routine. The RD will instruct the participants regarding standard of care lifestyle recommendations. This includes education of a low-calorie diet (500-1000 kcal) and moderate-intensity exercise.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Dr. Robert Min

Weill Medical College of Cornell University

Chief Executive Officer since 2024

MD, MBA

Dr. Adam R. Stracher

Weill Medical College of Cornell University

Chief Medical Officer since 2024

MD

Findings from Research

A 10-week diet plus exercise program significantly improved liver health and overall fitness in patients with nonalcoholic fatty liver disease (NAFLD), showing better results than exercise alone.

While both diet-plus-exercise and exercise-only programs improved health markers like body weight and insulin sensitivity, only the diet-plus-exercise group showed significant improvements in liver biochemistry, highlighting its greater efficacy in treating NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapeutic lifestyle program on ultrasound-diagnosed nonalcoholic fatty liver disease. Chen, SM., Liu, CY., Li, SR., et al.[2022]

Intermittent fasting has been shown to promote weight loss, reduce inflammation, and improve gut health, making it a promising dietary approach for managing obesity and metabolic syndrome.

While there is some evidence suggesting potential benefits of intermittent fasting for nonalcoholic fatty liver disease, more clinical studies are needed to confirm its safety and efficacy specifically for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review. Lavallee, CM., Bruno, A., Ma, C., et al.[2022]

The timing of energy intake throughout the day is crucial for liver health, with irregular meal patterns, skipping breakfast, and late-night eating linked to a higher risk of non-alcoholic fatty liver disease (NAFLD).

Intermittent fasting and time-restricted eating may improve metabolic health and benefit patients with NAFLD by restoring natural circadian rhythms, as supported by both observational studies and pilot human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD. Marjot, T., Tomlinson, JW., Hodson, L., et al.[2023]

Lifestyle changes, particularly optimizing nutrition and increasing physical activity, are crucial for improving or resolving non-alcoholic fatty liver disease (NAFLD).

Among various dietary interventions studied in 317 adults with NAFLD, the Mediterranean Diet showed the most significant reductions in liver fat and weight loss, indicating its potential effectiveness, although more research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review. Saeed, N., Nadeau, B., Shannon, C., et al.[2020]

In a study of 32 participants with non-alcoholic fatty liver disease (NAFLD), time-restricted fasting (TRF) for 16 hours daily led to significant reductions in liver fat (steatosis), weight, waist circumference, and BMI compared to standard care over 12 weeks.

TRF proved to be more effective than standard dietary advice, suggesting it could be a primary intervention for weight loss and management of NAFLD without requiring calorie restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial. Feehan, J., Mack, A., Tuck, C., et al.[2023]

In a 12-month clinical trial involving 88 participants with obesity and nonalcoholic fatty liver disease (NAFLD), both time-restricted eating (TRE) and daily calorie restriction (DCR) resulted in similar reductions in intrahepatic triglyceride (IHTG) content, indicating that TRE does not offer additional benefits over DCR for this condition.

Both TRE and DCR led to significant reductions in liver stiffness, body weight, and metabolic risk factors, emphasizing that caloric intake restriction is crucial for managing NAFLD, regardless of the eating pattern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. Wei, X., Lin, B., Huang, Y., et al.[2023]

Intermittent fasting has been shown to significantly reduce body weight, body mass index (BMI), and improve liver enzymes (ALT and AST) in adults with non-alcoholic fatty liver disease (NAFLD), based on a meta-analysis of six studies involving 417 patients.

While intermittent fasting appears effective for weight management and liver health, further research is needed to assess its long-term safety and feasibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Yin, C., Li, Z., Xiang, Y., et al.[2021]

In a study of 80 adults with obesity and non-alcoholic fatty liver disease (NAFLD), combining alternate day fasting (ADF) with exercise significantly reduced intrahepatic triglyceride (IHTG) content by 5.48% over 3 months, compared to minimal changes in the exercise and control groups.

While the combination of ADF and exercise improved liver health markers and body composition, it did not show significantly greater benefits compared to ADF alone, suggesting that fasting alone may be sufficient for reducing liver fat in NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial. Ezpeleta, M., Gabel, K., Cienfuegos, S., et al.[2023]

In a study of 3813 participants, those who practiced time-restricted eating (TRE) with a daily eating window of 8 hours or less had a 30% lower odds of developing non-alcoholic fatty liver disease (NAFLD) compared to those with a longer eating window.

The association between TRE and reduced NAFLD risk was found to be independent of physical activity and diet quality, and was particularly strong in individuals with lower energy intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study. Zeng, X., Xie, S., Jiang, F., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of therapeutic lifestyle program on ultrasound-diagnosed nonalcoholic fatty liver disease. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study. [2023]