Intermittent Fasting for Non-alcoholic Fatty Liver Disease

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Insulin, Sulfonylureas

Disqualifiers: Heavy alcohol use, Type II diabetes, Chronic liver disease, Chronic kidney disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is studying if time-restricted, intermittent fasting can help reduce liver fat in adults who are not obese. The idea is that fasting will make the body burn fat for energy instead of sugar, which might help decrease liver fat. Intermittent fasting has shown favorable effects on body weight and relevant indicators of liver health in several reports.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used any pharmacological treatments for NAFLD/NASH in the past 6 months, except for vitamin E. If you're on a stable dose of vitamin E, you can still join the study.

What data supports the effectiveness of the treatment Intermittent Fasting for Non-alcoholic Fatty Liver Disease?

Research shows that intermittent fasting, including alternate-day fasting, can help reduce liver fat and improve liver health in people with non-alcoholic fatty liver disease (NAFLD). Studies found that combining alternate-day fasting with exercise significantly reduced liver fat compared to exercise alone or no intervention. ^{1 2 3 4 5}

Is intermittent fasting safe for humans?

Intermittent fasting, including alternate-day fasting and time-restricted eating, has been studied in humans and is generally considered safe, showing benefits like weight management and improved liver enzymes. However, long-term safety data is still needed, so it's important to consult with a healthcare provider before starting any fasting regimen. ^{1 2 3 5 6}

How is intermittent fasting different from other treatments for non-alcoholic fatty liver disease?

Intermittent fasting, such as alternate-day fasting or time-restricted eating, is unique because it focuses on meal timing rather than specific foods or medications, offering a non-drug approach to reduce liver fat and improve metabolic health. Unlike standard treatments that may involve medication or continuous calorie restriction, intermittent fasting allows for periods of normal eating, which can be easier to maintain and has shown promising results in reducing liver fat and improving lipid profiles. ^{1 2 3 5 7}

Research Team

Eligibility Criteria

Adults with non-obese NAFLD (BMI between 23-30), confirmed by a recent liver assessment, who are not heavy drinkers, without other chronic liver diseases or severe illnesses. Participants must not be on weight loss treatments or have unstable body weight and should not be pregnant or trying to conceive.

Inclusion Criteria

Evidence of NAFLD confirmed by historical procedure obtained no more than 6 months prior to the screening visit, defined as:

Hepatitis C antibody and Hepatitis B surface antigen negative at screening

Willing and able to provide informed consent

Exclusion Criteria

Known positivity for human immunodeficiency virus infection

My kidney function is reduced with an eGFR below 60.

I have had a liver transplant or am on the liver transplant list.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a time-restricted, intermittent fasting diet for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Intermittent Fasting (Behavioral Intervention)

Trial Overview The trial is exploring the effects of Intermittent Fasting as a lifestyle treatment for adults with Non-alcoholic Fatty Liver Disease (NAFLD) who aren't obese. It aims to find non-drug methods to manage this condition.

Participant Groups

Group I: Time-Restricted, Intermittent Fasting Group Experimental Treatment 1 Intervention

Special type of diet for 6 weeks, called time-restricted, intermittent fasting.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

Findings from Research

A study involving 98 NAFLD patients showed that 16 hours of daily fasting during Ramadan significantly improved liver enzymes (ALT and AST) and lipid profiles, with some patients achieving normalization of ALT levels after one month of fasting.

Intermittent fasting also led to reductions in body mass index (BMI) and improvements in glycemic indices, indicating its potential as an effective lifestyle modification for managing NAFLD, especially in early phases and among prediabetic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients. Badran, H., Elsabaawy, M., Sakr, A., et al.[2022]

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 271 patients with non-alcoholic fatty liver disease (NAFLD), alternate-day fasting (ADF) led to significant weight loss and fat mass reduction within just 4 weeks, with continued improvements over 12 weeks.

ADF also resulted in a notable decrease in total cholesterol and triglycerides, indicating its potential effectiveness in improving lipid profiles in NAFLD patients, although further research is needed to confirm its long-term cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. Cai, H., Qin, YL., Shi, ZY., et al.[2020]

Fasting regimens may serve as a promising adjunctive treatment strategy for nonalcoholic fatty liver disease (NAFLD), which currently has no confirmed treatments.

The potential mechanisms by which fasting diets could benefit NAFLD include modulation of hepatic steatosis, signaling of fibroblast growth factors 19 and 21, and improvements in lipophagy and metabolic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fasting diets on nonalcoholic fatty liver disease. Mokhtari, Z., Hosseini, E., Hekmatdoost, A., et al.[2023]

Long-term alternate day fasting (ADF) significantly reduces hepatic inflammation and lipid accumulation in mice with high-fat diet-induced nonalcoholic fatty liver disease (NAFLD), suggesting its efficacy as a dietary intervention.

The protective effects of ADF against NAFLD are linked to the activation of PPARα and increased expression of fibroblast growth factor 21 (Fgf21), indicating a specific mechanism of action that could be targeted for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate-day fasting alleviates high fat diet induced non-alcoholic fatty liver disease through controlling PPARα/Fgf21 signaling. Liu, X., Zhang, Y., Ma, C., et al.[2022]

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 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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients. [2022]

2. 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]

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

Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. [2020]

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

The effects of fasting diets on nonalcoholic fatty liver disease. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Alternate-day fasting alleviates high fat diet induced non-alcoholic fatty liver disease through controlling PPARα/Fgf21 signaling. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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